Stimulation devices and methods

ABSTRACT

Described here are stimulation systems and methods for stimulating one or more anatomical targets in a patient for treatment conditions such as dry eye. The stimulation system may include a controller and a microstimulator. The components of the controller and microstimulator may be implemented in a single unit or in separate devices. When implemented separately, the controller and microstimulator may communicate wirelessly or via a wired connection. The microstimulator may generate pulses from a signal received from the controller and apply the signal via one or more electrodes to an anatomical target. In some variations, the microstimulator may include a passive generation circuit configured to generate a pulse based on a signal received from the controller.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.13/298,042, filed on Nov. 16, 2011, which claims priority to U.S.Provisional Application Ser. No. 61/414,293, filed on Nov. 16, 2010, toU.S. Provisional Application Ser. No. 61/433,645, filed Jan. 18, 2011,to U.S. Provisional Application Ser. No. 61/433,649, filed Jan. 18,2011, and to U.S. Provisional Application Ser. No. 61/433,652, filed onJan. 18, 2011. This application also claims priority to U.S. ProvisionalApplication Ser. No. 61/473,141, filed on Apr. 7, 2011, and to U.S.Provisional Application Ser. No. 61/523,732, filed on Aug. 15, 2011.Each of the foregoing applications is hereby incorporated by referencein its entirety.

FIELD

The present invention relates generally to stimulation systems andmethods of use thereof. The stimulation systems may be used to stimulateone or more anatomical structures for the treatment of one or moreindications, such as dry eye syndrome.

BACKGROUND

Dry eye syndrome is a debilitating disease that affects millions ofpatients worldwide and can cripple some patients. Millions of theseindividuals suffer from the most severe form. This disease ofteninflicts severe ocular discomfort, results in a dramatic shift inquality of life, induces poor ocular surface health, substantiallyreduces visual acuity and can threaten vision. Patients with severe dryeye develop a sensitivity to light and wind that prevents substantialtime spent outdoors, and they often cannot read or drive because of thediscomfort. Current treatment options provide little relief for thosesuffering from severe conditions. Current options include artificialtears, punctal plugs, humidity goggles, topical cyclosporine, andtarsorrhaphy. None of these treatments provides sufficient relief ortreatment of the disease. What is needed is a system for restoringadequate tear production in patients having dry eye syndrome.

BRIEF SUMMARY

Described here are devices and methods for stimulating tissues. Thestimulation systems may comprise a microstimulator and one or morecontrollers. In some variations, the microstimulator may comprise apassive stimulation circuit. In some variations, the microstimulator maycomprise a housing and an extension connected to the housing andcarrying at least one electrode. In some of these variations, theextension may be flexible. In some variations, the microstimulator mayhave a length of about 0.6 cm to about 2 cm, and a thickness of about 1mm to about 2 mm, and a width of about 3 mm to about 8 mm. Themicrostimulator may be conformable and flexible and may have one or morefixation elements. The one or more fixation elements may include one ormore hooks, barbs, and anchors. The microstimulator may have one or morecoatings which may be adhesive and/or bioabsorbable. In some variationsthe microstimulator may comprise one or more coatings that areelectrically conductive and/or electrically insulative.

The passive stimulation circuit may include a tank circuit and have oneor more electrical safety features. The electrical safety features mayinclude one or more current limiting rectifiers and one or more zenerdiodes. The electrical safety features may include a voltage limitingcircuit to limit the voltage emitted by the stimulation component. Theelectrical safety feature may also include a current limiting element orcircuit to limit the current emitted by the stimulation component and acharge output limiting element or circuit to limit the charge emitted bythe stimulation component.

In some variations the passive stimulation circuit may comprise aramping control unit. In some of these variations, the ramping controlunit may comprise a charging unit and a field-effect transistor. Theramping control unit may control the amplitude of the stimulation signalgenerated by the stimulation circuit, and the stimulation circuit may beconfigured to produce a ramped stimulation signal. The passivestimulation circuit may comprise a signal conditioning unit. In somevariations, the signal conditioning unit may comprise a rectifying unit.In some variations, the signal conditioning unit may comprise anamplitude limiting unit. In some variations, the signal condition unitmay comprise a current source unit. The passive stimulation circuit maycomprise a receiving unit and an output unit.

The passive stimulation circuit within a microstimulator may alsoinclude a variable resistive element, a variable capacitive element andone or more electrodes. The one or more electrodes of the passivestimulation circuit may be contact points, may be nestled within themicrostimulator, may be coupled to a flexible lead, and may be coupledto a rigid lead. The one or more electrodes may contain platinum,iridium, platinum iridium, iridium oxide, titanium nitride, tantalum, orcombinations thereof.

The micro stimulator may be coupled to a controller and be hermeticallysealed. The microstimulator may be injectable into a patient using adelivery system. The delivery system may comprise an insertion device(such as a 12 or larger gauge needle) and/or a dissection tool. Themicrostimulator may have one or more features to facilitate minimallyinvasive retrieval. The length and width of the microstimulator may beselected to permit placement of a portion of the microstimulatoradjacent to the lacrimal gland. The length and width of themicrostimulator may also be selected to permit placement of the entiremicrostimulator adjacent to the lacrimal gland and to permit placementof the microstimulator on, partially in, within or about the lacrimalgland.

In some variations, a method for treating dry eye by stimulating one ormore nerves that innervate lacrimal gland tissue includes implanting amicrostimulator adjacent to the lacrimal gland and applying stimulationto the lacrimal gland. The microstimulator may comprise a passivestimulation circuit comprising a ramping control unit. Themicrostimulator may be adjacent to the lacrimal gland and fullyimplanted within an orbit of a patient's eye. The microstimulator may bepositioned such that it directly contacts the lacrimal gland. Themicrostimulator may be positioned such that it partially penetrates intothe lacrimal gland. The microstimulator may be fully implanted into orcompletely within the lacrimal gland. The microstimulator may be fullyor partially implanted within the orbit of the eye.

The stimulation provided by the microstimulator may selectivelystimulate one or more nerves that innervate the lacrimal gland. Thestimulation may selectively stimulate the one or more nerves thatinnervate the lacrimal gland without causing movement of the eye,without stimulating the ocular muscles, and without stimulating thesuperior rectus, lateral rectus, levator palpebrae superioris, retina orcorresponding motor nerves. In some variations, the stimulation mayselectively stimulate autonomic efferent fibers of the lacrimal gland.The autonomic efferent fibers may be selectively stimulated over thesensory afferent fibers or the A-delta pain fibers or over the C painfibers. In some variations, the stimulation may selectively stimulateafferent fibers of the lacrimal gland, and may induce unilateral orbilatering tearing. In certain variations, the stimulation may stimulateonly the one or more nerves that innervate the lacrimal gland. In somevariations, the stimulation may selectively stimulate the acinar and/orductal cells of the lacrimal gland. The stimulation may stimulate acombination of acinar cells, ductals cells, efferent fibers, and/orafferent fibers of the lacrimal gland.

When implanted, the microstimulator may conform to the fossa for thelacrimal gland after implantation. The microstimulator may conform to anexterior aspect of a lacrimal gland after implantation. Implanting amicrostimulator may further include conforming the microstimulator to anexterior aspect of the lacrimal gland. After implantation, themicrostimulator may conform to an exterior aspect of the fossa for thelacrimal gland.

The microstimulator may be implanted using an insertion device. In somevariations, the insertion device is a 12 or larger gauge needle. Inother variations, the insertion device comprises a cannula. In somevariations, the insertion device may comprise a piston assembly, whichin some variations may be spring-powered. The microstimulator may beloaded into the insertion device, and the insertion device may beinserted into an insertion pathway. In some variations, using ananatomical landmark at the corner of the eye, a needle may be positionedin proximity to the lacrimal gland, and the microstimulator may bedeployed using the needle. Anatomical landmarks include, but are notlimited to, the lateral canthis, an eyelid margin, a palpebral lobe ofthe lacrimal gland, the orbital rim, a bony protuberance on thesuperior-lateral aspect of the orbit, the vascular bed, or the like. Insome variations, a microstimulator may be implanted by lifting theeyelid, forming an insertion pathway through the conjunctiva under theeyelid, and advancing the microstimulator into the insertion pathway.The insertion pathway may be formed using a dissection tool. In somevariations, the insertion pathway may be formed using a dissectionelement of an insertion tool. In some variations, the insertion pathwaymay be formed between the periosteum and the orbital bone. In othervariations, the insertion pathway may be formed between the periosteumand the lacrimal gland.

The stimulation may include a current having a pulse amplitude betweenabout 250 μA to about 25 mA. The stimulation may include a pulseamplitude, a pulse width, and a pulse frequency, and one or more of thepulse amplitude, pulse width, or pulse frequency which may be variedover the treatment period. The stimulation may have a pulse frequencybetween about 2 Hz to about 270 Hz, between about 15 Hz to about 40 Hz,or between 30 Hz to about 60 Hz. The stimulation may include a currenthaving a pulse width between about 50 μsec to about 2700 μsec.Stimulation having the above-mentioned parameters may be used to treatone or more conditions, such as dry eye. Stimulation pulses may bedelivered continuously or intermittently, and may be delivered accordingto one or more patterns.

Implanting a microstimulator may further include identifying aninsertion point for implantation based upon a feature of the orbit. Thestimulation may be delivered in bursts and adjusted in response to ameasured variable. The stimulation may include a current having a pulsewidth between about 50 μsec to about 2000 μsec. A controller may bepositioned in proximity to the microstimulator and may generate amagnetic field. The magnetic field may be adjusted based on input fromthe user and/or based on the degree of coupling to the microstimulator.The magnetic field may be generated in bursts and coupled to themicrostimulator to generate the stimulation. The magnetic field may havea frequency of about 10 kHz to about 100 MHz. The magnetic field mayhave a frequency of about 100 kHz to about 5 MHz. In some variations,the magnetic field may have a frequency between about 1 MHz and about 5MHz.

In some variations, a system for treating dry eye may include amicrostimulator configured for implantation into an orbit of an eye anda controller for generating a magnetic field to couple to themicrostimulator. The controller may be housed within a hand-held device.The controller may comprise a patch which may be attached to a patientusing one or more adhesive layers. The controller may be flexible andconformable, or may be partially flexible or comfortable. The controllermay be coupled to, or at least partially contained within, a flexible orconformable material. The microstimulator may have a length of about 0.6cm to about 2 cm and a width of about 1 mm to about 8.5 mm and mayinclude a passive stimulation circuit configured to receive the magneticfield generated by the controller. The controller may be flexible,conformable, and capable of detecting one or more operating parametersof the microstimulator. At least part of the controller may bedisposable and rechargeable. The controller may be coupled to, or atleast partially contained within, an eyeglass frame, a wrist watch, orother object. In some variations, the controller may be configured toattach to an eyeglass frame using one or more adhesive layers and/ormechanical coupling elements.

In some variations, a method for treating dry eye by stimulating one ormore nerves that innervate lacrimal gland tissue may include positioningone or more stimulation electrodes adjacent to the lacrimal gland andapplying stimulation to the lacrimal gland. A microstimulator may beadjacent the lacrimal gland fully implanted within an orbit of apatient's eye. The microstimulator may be adjacent to and directlycontacting the lacrimal gland, adjacent to and at least partiallypenetrating into the lacrimal gland, and adjacent to and fully implantedinto or completely within the lacrimal gland. Adjacent to the lacrimalgland may be about, within or partially in the lacrimal gland. Themicrostimulator may be fully implanted within the orbit of the eye. Theone or more electrodes are electrically coupled to a pulse generator,which may be implantable. The pulse generator may be implantable inproximity to the one or more stimulation electrodes. The pulse generatormay be implantable in proximity to the temporal bone, a subclavicularpocket, or a subcutaneous abdominal pocket. The method may furtherinclude positioning a controller in proximity to the pulse generator.

In some variations, a microstimulator may include a coil, a housing, anda pair of electrodes. The coil may be formed from a wire having a lengthturned into a plurality of windings and responsive to an induced fieldto produce an output signal. The microstimulator may be electricallycoupled to receive the output from the coil and produce a signalresponsive to the output. The housing may encompass the circuit and thecoil, and may be adapted and configured for placement within an orbitand adjacent an eye within the orbit. The pair of electrodes may extendfrom the housing and be configured to receive the signal. In somevariations, the electrodes may be integrated into the housing. Theelectrodes may have the same shape or may have different shapes. In somevariations, one electrode may have a larger surface area, which mayreduce the current density at that electrode. The electrodes may bespaced apart (e.g., by about 6 mm to about 15 mm), which may increasecurrent flow through surrounding tissue. When positioned near thelacrimal gland, one or more of the electrodes may be placed in direct orindirect contact with the lacrimal gland.

The pair of electrodes and the housing may be shaped for injectionthrough the lumen of an insertion device. The housing may be configuredfor placement adjacent to a lacrimal gland, within an orbit to permitselective stimulation of a lacrimal gland with the signal, and within afossa near the lacrimal gland to position the pair of electrodes on, inor about a lacrimal gland.

The housing may be configured for placement in proximity to a lacrimalgland without being in proximity to a muscle of the eye. The housing mayhave a curvature conforming at least partially to the curvature of afossa for the lacrimal gland, or a curvature conforming at leastpartially to an exterior aspect of a lacrimal gland.

The microstimulator may further include a second coil, a secondrectifying and tuning circuit. The second coil may be within the housingand oriented nearly orthogonal to the second coil. The second rectifyingand capacitive circuit may be within the housing and coupled to thesecond coil, such that the second rectifying and capacitive circuit isconfigured to produce a second signal. The selector switch may be withinthe housing and connected to receive the first signal and the secondsignal and supply one of the first signal and the second signal to thepair of electrodes. The selector switch may determine which one of thefirst signal and the second signal to send to the electrodes based on acomparison of the first signal and the second signal.

Current from the two signals may be summed without the use of a selectorswitch. The signal from the coil may have a frequency corresponding tothe induced field, which may be generated from an external coil throughmutual inductance. The induced field may be generated by an externalcontroller.

The signal generated in the coil may have a frequency about equal to thefrequency of the induced field generated by the external controller. Theinduced field generated by the external controller may have a frequencybased on user input. The external controller may be contained within ahand-held device and may be disposable. The external controller may becontained within one of an adhesive patch, a pair of eye glasses, and ahead set. The circuit may include a diode to rectify a current signaland a capacitor for storing charge and/or filtering the rectifiedsignal. The circuit may include a rectifying circuit that may include adiode and a resistor connected in parallel. The signal may have avoltage with an amplitude of between 0.1V and 25V, a current with anamplitude between 10 μA and 25 mA, and a pulsed current with a frequencyof 2 Hz to 1000 Hz. The pair of electrodes may be connected to leads,which may include tines.

In some variations, a method of implanting a microstimulator adjacent tothe eye may include inserting an access device percutaneously into anorbit of an eye. A microstimulator may be advanced through the accessdevice into a position in proximity to the superior lateral aspect ofthe orbit. A stimulation signal may be applied to a portion of the eyewith the microstimulator. Before the inserting step, an insertion pointmay be inserted for the access device based on the insertion point'srelation to a feature on the orbit. After the advancing, themicrostimulator may be positioned within a fossa of the lacrimal gland,and at least one electrode of the microstimulator may be positioned on,in or adjacent to a lacrimal gland, and an electrode of themicrostimulator is positioned on, in or adjacent a lacrimal gland.

Tear production may be increased in the eye. Vasodilation of thelacrimal gland may occur unilaterally or bilaterally. After advancing,an electrode of the microstimulator may be positioned on, in or adjacentto a neural structure associated with a lacrimal gland. During theapplying, the signal only stimulates a lacrimal gland, the signal mayselectively stimulate a lacrimal gland over a muscle of the eye, or thesignal is selected to stimulate a lacrimal gland without stimulating amuscle fiber of the eye. After the advancing, an electrode of themicrostimulator is positioned adjacent to a neural structure associatedwith a lacrimal gland and spaced apart from a muscle of the eye. Themuscle of the eye may be a rectus muscle or an oblique muscle or alevator palpebrae muscle. The microstimulator may be adjacent a lacrimalgland and spaced apart from a superior rectus muscle or a lateral rectusmuscle or a levator palpebrae muscle. The signal may stimulate alacrimal gland without activating a rectus muscle or an oblique muscleor a levator muscle in proximity to the lacrimal gland.

In some variations, a method for using a microstimulator may includereceiving a microstimulator at the orbit of a patient's eye. A magneticfield may be received by the microstimulator from an external powersource such as a controller. A current may be generated by themicrostimulator from the magnetic field. The current may be applied tothe patient to produce tears in the patient's eye or vasodilation of thelacrimal gland.

In some variations, a method for using a microstimulator may includeimplanting a stimulation device within a patient's orbit. A controllerwith a power source may be placed external to the patient's skin and incommunication with the microstimulator. A magnetic field may be appliedto the microstimulator from the controller. A current may be generatedin the microstimulator from the magnetic field. The current may beapplied to produce tears in the patient's eye, cause vasodilation in thelacrimal gland, release lacrimal proteins into a patient's tear film,and/or cause lacrimation of the contralateral lacrimal gland.

In some variations, a system for treating a patient with dry eyesyndrome may include a microstimulator and a controller. Themicrostimulator may be responsive to a magnetic field and placed withinan orbit of a patient's eye. The microstimulator may be configured togenerate a current based on the magnetic field and apply the current toa patient to produce tears in the patient's eye. The controller may beconfigured to generate the magnetic field and be placed at a locationnear the microstimulator.

In some variations, a method for treating a patient with dry eyesyndrome may begin with insert a microstimulator within an orbit of apatient's eye using a positioning device. A controller, which mayinclude a power source, may be placed external to a patient's skin andin proximity to the microstimulator. A magnetic field may be applied tothe microstimulator by the controller. A current may be generated by themicrostimulator from the magnetic field. The current may then be appliedto a patient to produce tears in the patient's eye. In some variations,a method for using a microstimulator may begin with connecting amicrostimulator to a multi-electrode lead positioned on, in or adjacenta lacrimal gland. One or more electrodes may be selected from themulti-electrode lead to activate tear production in a patient's eye.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B depict block diagrams of two variations of thestimulation systems described here.

FIG. 2 depicts an illustrative variation of a passive stimulationcircuit that may be used with the stimulation devices described here.

FIGS. 3A-3F depict illustrative variations of coil arrangements suitablefor use with the microstimulators described here.

FIGS. 4, 5A and 5B depict variations of passive stimulation circuitssuitable for use with the microstimulators described here.

FIGS. 6A-6H depict exemplary microstimulators suitable for use with thestimulation systems described here.

FIGS. 7A-7F depict illustrative microstimulators having differentelectrode configurations.

FIGS. 8A and 8B depict one variation of a microstimulator that isconfigured to change shape upon release from a delivery device.

FIGS. 9A, 9B, 10, 11A and 11B depict variations of microstimulatorssuitable for use with the stimulation systems described here.

FIGS. 12, 13, and 14 depict variations of microstimulators havingfixation elements.

FIGS. 15A-15C depict variations of microstimulators comprising retrievalfeatures.

FIGS. 16A-16C depict variations of controllers suitable for use with thestimulation systems described here.

FIGS. 17A, 17B, 18, 19, 20, 21, 22, 23A and 23B depict variations ofcontrollers suitable for use with the stimulation systems describedhere.

FIGS. 24, 25A, 25B, and 26 depict illustrative variations of controllersets suitable for use with the stimulation systems described here.

FIGS. 27A and 27B are perspective views of the lachrymal apparatus.FIGS. 27C and 27D are front views of the skull of a patient.

FIG. 28 depicts a flow chart of a stimulation method described here.

FIGS. 29A-29H depict different implantation locations for themicrostimulators described here.

FIG. 30 depicts a block diagram of a variation of a controller suitablefor use with the stimulation systems described here.

FIGS. 31A-31D depict different variations of microstimulators implantednear the lacrimal gland.

FIG. 32 depicts an example of an implantation location for themicrostimulators described here.

FIG. 33 depicts one variation of the microstimulators described hereimplanted in a lacrimal duct.

FIG. 34 depicts one variation of a method by which a microstimulator maybe delivered to a patient.

FIGS. 35A and 35B depict side views of a variation of an insertiondevice suitable for use with the delivery systems described here.

FIG. 36 shows a block diagram of one variation of a passive stimulationcircuit for use with the microstimulators described here.

FIG. 37 shows a variation of a microstimulator suitable for use with thestimulation systems described here.

FIG. 38 depicts a variation of an insertion device suitable for use withthe delivery systems described here.

FIG. 39 depicts a variation of a dissection tool suitable for use withthe delivery systems described here.

FIGS. 40A-40D depict a method of delivering a microstimulator to theocular cavity.

FIG. 41 depicts a variation of a guiding element suitable for use withthe delivery systems described here.

FIGS. 42A-42C depict a perspective view, a side view, and a partialview, respectively, of a variation of a microstimulator suitable for usewith the stimulation systems described here.

FIG. 43 illustrates a variation of a passive stimulation circuitsuitable for use with the microstimulators described here.

FIG. 44 depicts a variation of a controller suitable for use with thestimulation systems described here.

FIGS. 45A, 45B, and 46 illustrate variations of controller circuitssuitable for use with the controllers described here.

DETAILED DESCRIPTION

Described here are stimulation systems for stimulating anatomicaltargets in a patient for the treatment of one or more conditions. Thestimulation systems may include at least one controller and at least onemicrostimulator. The controller may be implemented as a part of themicrostimulator, or as a separate device. When formed as a separatedevice, the controller may communicate with the microstimulator via awireless and/or wired connection. The controller may produce a waveformsignal which may convey power and/or information to the microstimulatorand the microstimulator may deliver one or more stimulation signals toan anatomical target based on the waveform signal.

The stimulation systems may be used to stimulate any suitable anatomicaltarget or targets to treat a number of conditions. In some variations,the stimulation systems described here may be used to treat dry eye. Forexample, the stimulation systems may be used to stimulate one or morenerves, tissues, glands, or other structures involved in the process oflacrimation or glandular vasodilation. For example, the systems maystimulate one or more of a lacrimal gland, one or more meibomian glands,lacrimal ducts, parasympathetic nerves, fibers and neurites, sympatheticnerves, fibers and neurites, rami lacrimales, lacrimal nerve,perivascular nerves of lacrimal artery and branches thereof, nervefibers innervating the meibomian glands, myoepithelial cells of thelacrimal gland, acinar cells of the lacrimal gland, ductal cells of thelacrimal gland. Methods of treating dry eye and other conditions aredescribed in more detail below. Also described here are delivery systemsand methods for delivering or otherwise implanting one or moremicrostimulators and/or controllers into a patient.

Stimulation Systems

FIGS. 1A and 1B show block diagrams of two variations of the stimulationsystems described here. FIG. 1A depicts a wireless stimulation system(100) including a controller (110) and a microstimulator (120). As shownthere, the controller (110) may include a housing (119) and may containa controller circuit (115). The controller circuit (115) may generateand transmit an output signal (112), which may be received wirelessly bythe microstimulator (120). The transmitted signal may include one ormore magnetic fields, electronic signals, radiofrequency signals,optical signals, ultrasound signals, or the like. The output signal(112) may provide power and/or information to the microstimulator (120)as will be described in more detail below. The controller may beimplanted within the patient, or may remain external patient, as will bedescribed in more detail below. The controller circuit (115) may be anysuitable circuit, such as one or more of the controller circuitsdescribed in more detail below.

As shown in FIG. 1A, the microstimulator (120) may include one or moreelectrodes (117), one or more leads (113), and a stimulation circuit(121). While the electrodes (117) are shown in FIG. 1A as beingconnected to the stimulation circuit (121) via leads (113), it should beappreciated that the microstimulator (120) need not include leads. Themicrostimulator (120) may be implanted within a patient and positionedwith respect to the controller (110) whereby the microstimulator (120)may receive the output signal (112) generated by the controller (110).The stimulation circuit (121) may receive the output signal (112), andmay generate a stimulation signal (114) based on the received outputsignal (112). For example, in some variations the microstimulator (120)may comprise a passive stimulation circuit that is configured to processthe output signal (112) and deliver the processed signal as astimulation signal (114) to tissue without using any internal logic orintelligence within the microstimulator (120). In some variations, themicrostimulator (120) may use internal logic or intelligence inprocessing the received output signal (112). The resulting stimulationsignal (114) may be a direct current or alternating current signal, andmay be applied to an anatomical target (123), such as for example alacrimal gland, via one or more of the electrodes (117). The stimulationsignal (114) may be charge-balanced. The microstimulator may beconfigured in any suitable manner, as will be described in more detailbelow.

When the stimulation signal (114) is delivered to an anatomical target(123), the stimulation may result in a desired physiological effect(such as, for example, generating tears in a patient). Stimulation of ananatomical target (123) may produce any suitable endocrinological orother physiological outcome, including, but not limited to, secretion offluid, electrolytes, and proteins, vasodilatation, increasing the volumeof tears, increasing the quality of tears, improving surface health,decreasing tear osmolarity, and decreasing ocular inflammation.

FIG. 1B shows a block diagram of a variation of a wired stimulationsystem (130). The wired stimulation system (130) may include acontroller (140) and a microstimulator (150). The controller (140) mayinclude a housing (149) and a controller circuit (145), and may beconfigured to transmit an output signal (142) to the microstimulator(150) via a wired transmission line (148), such as a conducting wire orother medium. The wired transmission line (148) may be attached to thecontroller (140) and be routed through a patient's body to themicrostimulator (150). The microstimulator (150) may be implanted withina patient and positioned with respect to the controller (140) such thatthe microstimulator (150) may receive the output signal (142) from thecontroller (140). The stimulation circuit (151) may receive the outputsignal (142), and may generate a stimulation signal (144) based on thereceived output signal (142). The stimulation signal (144) may beapplied to an anatomical target (153), such as for example a lacrimalgland, via one or more of the electrodes (147) and, in some instances,one or more leads (143). Stimulation of the anatomical target (153) mayresult in one or more physiological or other endocrinological outcomes(159), such as those described immediately above.

When the stimulation systems comprises a transmission line between acontroller and microstimulator, or a lead connecting one or moreelectrodes to a microstimulator, the transmission line and/or leads maybe tunneled. The tunneling pathway may depend on where themicrostimulator, controller, and/or electrodes are implanted. Forexample, a tunneling pathway may extend from the ear region (superficialto the temporal bone) to the temporal aspect of the orbit into thesuperior lateral aspect of the orbit, through the orbital septum and tothe anatomical target.

Microstimulators

As mentioned above, the stimulation systems described here comprise oneor more microstimulators. The microstimulator may be any device suitablefor delivering stimulation to tissue. In some variations, themicrostimulator may comprise one or more passive stimulation circuits inwhich the device does not include any internal logic or intelligence(e.g., ASICs, microcontrollers or the like). In some of thesevariations, the microstimulator does not have an internal battery. Inthese variations, the microstimulator may include only a dissipationcircuit that receives an output signal from a controller, generates acurrent based on the received signal, and delivers the generatedcurrent. The dissipation circuit may contain one or more signalconditioning units which may shape or otherwise modify the signalreceived from a controller. In some variations, the circuit may beconfigured to receive energy from an external source, rectify the energyinto a stimulation pulse, and allow for passive charge balancing. Insome variations the stimulation circuit may comprise one or more currentrectifiers, one or more amplitude limiting units, and one or moreramping control units, combinations, thereof, or the like. In somevariations, the dissipation circuit may comprise one or moreadjustable/tunable components.

In other variations, a microstimulator may include internal logic whichmay be used to shape or modify a signal received from a controller. Insome of these variations, the microstimulator may not include aninternal battery, such that operating power is received by the outputsignal of a controller. In still other variations, the microstimulatormay comprise an implantable pulse generator, which may include all ofthe circuitry necessary to generate and deliver electrical pulses totissue. The stimulation circuits described here may contain elementswhich allow a controller to detect one or more operating parameters ofthe stimulation circuit.

FIG. 2 depicts one variation of a passive stimulation circuit (200)which may be used with the stimulation devices described here. As shownthere, the stimulation circuit (200) may include a microstimulator coil(202) (e.g., a conductive coil), a rectifying circuit (205) including adiode (204) and a resistor (206), a tuning capacitor (208), and acoupling capacitor (216). As shown there, one end of the microstimulatorcoil (202) may be connected to a first end of tuning capacitor (208),and a first end of the rectifying circuit (205). The resistor (206) anddiode (204) may be connected in parallel, with a first end of therectifying circuit (205) connected to the tuning capacitor (208) and themicrostimulator coil (202) and the second end of the rectifying circuit(205) connected to the coupling capacitor (216). The coupling capacitor(216) may be connected to a first electrode (210). It should beappreciated that the rectifying circuit (205) may comprise a half-waverectifier, a full-wave rectifier, or the like. The second end ofmicrostimulator coil (202) may be connected to the other end of thetuning capacitor (208) and a second electrode (212).

In operation, a magnetic field generated by a controller (not shown) maybe applied to microstimulator coil (202). The microstimulator coil (202)may generate a current i_(coil) as a result of the applied magneticfield (e.g., via inductive coupling). The tuning capacitor (208) mayform a tuning circuit with the microstimulator coil (202) such that themicrostimulator coil (202) only receives magnetic fields generated usinga specific frequency or range of frequencies. The current may passthrough the rectifying circuit of resistor (208) and diode (204) anddeliver a current i_(load) between first (210) and second (212)electrodes. The current i_(load) may pass through tissue (214)(represented in FIG. 2 as a resistor). The coupling capacitor (216) mayprovide AC-coupling and charge-balancing for the stimulation applied tothe tissue (214). The coupling capacitor (216) may charge when an activestimulation pulse is passed through the rectifying circuit (205), andmay discharge through the resistor (208) of the rectifying circuitduring an inactive phase following the delivery of the activestimulation pulse.

Because the passive stimulation circuit is configured to condition anddeliver the output signal received from a controller, one or morecharacteristics of the stimulation signal delivered by a microstimulatormay be at least partially dependent on one or more characteristics ofthe stimulation signal. The controller may adjust one or morecharacteristics of the output signal (e.g., the amplitude, burst width,burst frequency, etc.) to alter the one or more characteristics (e.g.,amplitude, pulse width, pulse frequency, etc.) of the stimulation signalproduced by the microstimulator. For example, the amplitude of a signalapplied generated by a microstimulator may be adjusted by modifying theamplitude of an alternating magnetic field produced by a controllercoil.

While the stimulation circuit (200) is shown in FIG. 2 as comprising acoil (202), it should be appreciated that the stimulation circuitsdescribed here may receive energy in any suitable manner. For example,in some variations the stimulation may be configured to receive magneticenergy. In these variations, the microstimulator may comprise one ormore coils (such as shown in FIG. 2) and/or magneto-electrical elementswhich may be formed from a material that generates a current when amagnetic field is applied thereto. The magneto-electrical elements maybe formed from one or more materials such as Cr₂O₃, one or moremutiferroic materials, combinations thereof and the like.Magneto-electrical elements may allow for current generation with asmaller volume or device footprint than may be required for a coil. Themagneto-electrical elements may further be shaped such that it may becapable of generating a current when positioned in multiple orientationsrelative to a magnetic field.

In some variations, the stimulation circuit may be configured to receiveultrasound energy. For example, in some variations the microstimulatormay comprise one or more ultrasound transducers which may generatecurrent in response to a transmitted ultrasound signal. In somevariations, the ultrasound signal may be focused on the microstimulatorusing one or more ultrasound transmitters. In other variations, themicrostimulator may be configured to receive optical energy (e.g.,infrared, ultraviolet, visible wavelengths, or the like) and generate acurrent in response thereto. For example, in some variations astimulation circuit may comprise one or more photo-voltaic elements thatgenerate a current in response to received optical energy. In othervariations, the microstimulator may be configured to receive far-fieldRF energy. For example, high-frequency RF energy may be received by themicrostimulator using an antenna, and may allow for tolerate for avariety of microstimulator orientations. It should be appreciated thatin some variations, the microstimulators described here may be capableof receiving energy from a plurality of sources, such as a combinationof magnetic, ultrasound, optical, and/or RF signals.

In variations where a stimulation circuit is configured to generate acurrent using inductive coupling, the stimulation circuit may beconfigured to improve tolerance to angular misalignment between internaland external components. In some of these variations, a microstimulatormay include two or more coils positioned in non-parallel orientations.FIGS. 3A-3F illustrate three variations of coil arrangements havingmultiple coils. For example, FIGS. 3A and 3B show a side view and a topview, respectively, of a coil arrangement (300) comprising a first coil(302) and a second coil (304). As shown there, the first coil (302) maybe positioned in a plane that is at an angle (θ₁) relative to a plane ofthe second coil (304). The angle (θ₁) between the planes of the firstand second coils is shown in FIGS. 3A and 3B as being approximately 90degrees, but it should be appreciated that this angle may be anysuitable angle (e.g., about 45 degrees, about 60 degrees, etc.). Bypositioning the coils in different planes, the coil arrangement maystill be able to generate a current even if one of the coils ispositioned perpendicularly to an external coil.

FIGS. 3C and 3D illustrate a side view and a top view, respectively, ofanother variation of a coil arrangement (306) having a first coil (308),a second coil (310), and a third coil (312). The planes of each of thefirst (308), second (310), and third (312) coils may be angled relativeto other coils. For example, in the variation shown in FIGS. 3C and 3D,the plane of the first coil (308) may be perpendicular to the plane ofthe second coil (310), and the plane of the third coil (312) may beperpendicular to the planes of both the first (308) and second coils(310). It should be appreciated that the angle between any of the twocoils may be any suitable angle. FIGS. 3E and 3F depict a perspectiveview and a side view, respectively, of another variation of a coilarrangement (314) having a first coil (316), a second coil (318), and athird coil (320). The planes of each of the first (316), second (318),and third (320) coils may be angled relative to the other coils, asdescribed immediately above. Additionally, to help reduce the overallprofile of the coil arrangement (314), the first coil (316) may bepositioned within the second coil (318), and the first (316) and second(318) coils may be positioned within the third coil (320). In instanceswhere a stimulation circuit comprises a coil arrangement comprising aplurality of coils, the stimulation circuit may comprise a plurality oftuning circuits, and the currents produced by the plurality of coils maybe summed using rectifiers.

While the passive stimulation circuit (200) described above with respectto FIG. 2 as being configured to deliver electrical stimulation to apatient, it should be appreciated that the microstimulators describedhere may be configured to apply any suitable stimulation to a patient.In some variations, a microstimulator may be configured to deliver oneor more optical signals, acoustic signals, or the like to a patient.

The stimulation circuits described here may comprise one or moreelectrical safety features. The electrical safety features may limit oneor more parameters of the signals received or generated by themicrostimulator, which may prevent a potentially harmful stimulationcircuit from being supplied to a patient. Electrical safety features mayinclude one or more elements such as a capacitor in series with theelectrodes to limit charge delivery, one or more elements such as acapacitor in series with the electrodes to ensure DC charge-balancedstimulation, one or more resistors in parallel with the electrodesand/or series capacitor to allow for DC charge-balanced stimulation bycapacitive discharge, one or more current-limiting diodes in series withthe electrodes to limit maximum stimulation current amplitude, one ormore zener diodes to limit maximum output voltage, combinations thereofor the like. The resistor in parallel with the electrodes may be of alarger impedance than the tissue load impedance to ensure powerefficient stimulation.

FIG. 4 shows one variation of a stimulation circuit (400) comprising acurrent-limiting device. As shown there, stimulation circuit (400) maycomprise a coil (402), a tuning capacitor (404), and a rectifyingcircuit (405) consisting of a diode (406) and a resistor (408), andfirst (414) and second (416) electrodes. These elements may be the sameas the components of stimulation circuit (200) and may be positioned asdescribed above in relation to FIG. 2. Additionally shown in FIG. 4 is acurrent-limiting diode (412), where the current-limiting diode (412)separates the second electrode (416) from the coil (402) and tuningcapacitor (404). Current limiting diode (412) may limit the current thatpasses through the diode (412), which may also limit the current that ispassed through a tissue load (410) between first (414) and second (416)electrodes. For example, when a pulse is delivered through the tissueload (410), as will be described in more detail below, a rechargecurrent that provides charge balancing may initially have an amplitudethat causes discomfort or stimulation of unintended tissues. Acurrent-limiting device (or one or of the electrical safety featuresdescribed above, such as a high-impedance recharge circuit or a zenerdiode or voltage limiting element in parallel with the tissue load) maylimit the magnitude of the recharge current, and may thereby preventunintended tissue stimulation or discomfort/pain.

In some variations, the stimulation circuits described here comprisesone or more adjustable elements. For example, the stimulation circuitmay comprise one or more variable resistance elements, variablecapacitive elements, variable inductance elements, variable non-linearelements, or the like. The variable resistive elements, capacitiveelements, inductive elements, or nonlinear elements may be used to altera characteristic of the stimulation circuit, such as the resonantfrequency, or stimulation parameter such as for example amplitude. Invariations that include a variable component, the variable componentsmay be reversibly varied, or irreversibly varied. In some instances, oneor more of the variable components may be controlled and varied by anexternal controller, as described in more detail below. The variablecomponents may be adjusted to adjust or otherwise alter one or morefunctions of the microstimulator. For example, an adjustable element maybe used to alter the resonant frequency of a receiving unit or outputunit of the microstimulator, which may control the frequency of outputsignals that the receiving unit is capable of receiving and thefrequency of stimulation signals generated by the microstimulator.Additionally or alternatively, an adjustable element may be used toalter one or more parameters of stimulation provided by amicrostimulator (e.g., amplitude, pulse width, etc.).

Any of the components of the stimulation circuits described here may beadjustable. For example, in some variations the tuning capacitor (208)from the stimulation circuit (200) may be tuned to adjust the output ofthe stimulation circuit (200). FIGS. 5A and 5B show two examples ofstimulation circuits comprising adjustable elements. FIG. 5A shows avariation of stimulation circuit (500). As shown there, stimulationcircuit (500) may comprise a coil (502), a tuning capacitor (504), and arectifying circuit (505) consisting of a diode (506) and a resistor(508), first (514) and second (516) electrodes, and a current limitingdiode (512). These elements may be arranged as described above inrelation to FIGS. 2 and 4. Additionally shown there is a variableelement (518) positioned in series between the rectification circuit andthe first electrode (514). The variable element (518) may comprise avariable impedance element such as an opto-FET, an optically tunableresistor, a capacitor, a programmable current limiter, or the like. Thevariable element (518) may be adjusted (e.g., via a controller) to alterthe current that flows therethrough, which may alter the current that isdelivered through a tissue load (510) between the first (514) and second(516) electrodes. FIG. 5B shows another variation of a stimulationcircuit (520), which includes the same components as FIG. 5A, butwherein the variable element (518) is positioned in parallel with thefirst (514) and second (516) electrodes.

In some variations, a microstimulator may comprise a passive stimulationcircuit configured to passively ramp up the amplitude of stimulationsignal that is supplied to the patient during stimulation. In some ofthese variations, the passive stimulation circuit may further beconfigured to limit the maximum amplitude of the stimulation signalprovided to the patient. FIG. 36 shows a block diagram of one variationof a passive stimulation circuit (3600) which may be configured topassively ramp up the stimulation signal produced by the stimulationcircuit. As shown there, the passive stimulation circuit (3600) maycomprise a receiving unit (3602), a signal conditioning unit (3603), aramping control unit (3608), and an output unit (3610). The signalreceiving unit (3602) may receive one or more output signals from acontroller, which may be used to power the signal conditioning unit(3603) and the ramping control unit (3608). In some variations, thesignal receiving unit (3602) may be a tuned circuit, such that thesignal receiving unit (3602) only receives output signals of a certainfrequency or range of frequencies.

The signal conditioning unit (3603) may include an amplitude limitingunit (3604) and a rectification unit (3606), although it should beappreciated that the signal conditioning unit (3606) may comprise anycombination of units which may shape or otherwise alter the outputsignal received by the receiving unit (3602). In variations where thesignal conditioning unit (3603) comprises a rectification unit (3606),the rectification unit (3606) may rectify the signal being received bythe signal receiving unit (3602), and may comprise a full-wave rectifieror a half-wave rectifier. In variations that include an amplitudelimiting unit (3604), the amplitude limiting unit (3604) may limit theamplitude of the stimulation current that is delivered to tissue. Forexample, the amplitude limiting unit (3604) may comprise one or morezener diodes, current limiting elements, or the like, which may clip orotherwise limit the amplitude of the signals within the stimulationcircuit. For example, in some variations the output signal produced by acontroller may be larger than the intended stimulation signal amplitudeto account for potential alignment differences between the output stageof the controller and the receiving unit of the microstimulator. Inthese variations, an amplitude limiting unit (3604) may clip the excesspower received by the receiving unit (3602). While shown in FIG. 36 asbeing included in the signal conditioning unit (3603), it should beappreciated that an amplitude limiting unit (3604) may be included inany unit of the stimulation circuit (3600).

The signal conditioning unit (3603) may provide the conditioned outputsignal to output unit (3610), which may deliver a stimulation signal totissue via one or more electrodes. The amplitude of the stimulationsignal delivered to the output unit (3610) from the signal conditioningunit (3603) may be at least partially controlled by the ramping controlunit (3608). In some variations, the ramping control unit (3608) maycomprise a charging unit (3612) and a field-effect transistor (3614).The signal conditioning unit (3603) and the output unit (3610) may beconnected to the source and drain terminals of the field-effecttransistor (3614), and the charging unit (3612) may be connected to thegate terminal of the field-effect transistor (3614). The voltageprovided by the charging unit (3612) to the field-effect transistor(3614) may determine the current that flows between the signalconditioning unit (3603) and the output unit (3610). For example, whenthe charging unit (3612) is uncharged (which may occur when thereceiving unit (3602) initially begins receiving an output signal from acontroller), the field-effect transistor (3614) may prevent current flowbetween the signal conditioning unit (3603) and the output unit (3610),thereby preventing delivery of a stimulation signal to the patient. Asthe receiving unit (3602) provides power to the charging unit (3612),the voltage provided to the gate of the field-effect transistor (3614)increases (e.g., by charging a chargeable component, as will bedescribed in more detail below), which increases the amount of currentthat may flow between the signal conditioning unit (3603) and the outputunit (3610). Accordingly, the amplitude of the stimulation signalprovided by the output unit (3610) may increase as the charging unit(3612) charges, and the amplitude of the stimulation signal mayautomatically be ramped upward until the charging unit (3612) is fullycharged. The speed of this ramping may be determined by the rate atwhich the charging unit (3612) is charged. Additionally, the chargingunit (3612) may be configured to discharge when power is not beingsupplied thereto. This may allow the ramping unit (3602) to resetbetween different treatment sessions, such that the stimulation circuitcan ramp subsequent stimulation signals produced in subsequenttreatments.

FIG. 43 depicts a variation of a stimulator circuit (4320) which may beconfigured to passively ramp a stimulation signal provided by thestimulation circuit. As shown there, stimulator circuit (4320) maycomprise a receiving unit (4322), a signal conditioning unit (4324), aramping control unit (4326), and an output unit (4328). As described inmore detail above with respect to FIG. 36, the receiving unit (4322) maybe configured to receive an output signal from a controller (not shown),and may transmit the received signal to the signal conditioning unit(4324) and the ramping control unit (4326). In the variation shown inFIG. 43, the receiving unit (4322) may comprise a resonant circuitcomprising a coil (4330) connected in parallel with a tuning capacitor(4332). This resonant may be tuned or otherwise configured to receive anoutput signal that is transmitted at a certain frequency or range offrequencies. It should be appreciated, however, that the receiving unit(4322) may comprise any suitable components that receive an outputsignal (e.g., a magnetic field, RF signal, optical signal, ultrasoundsignal, or the like) and generate a current or voltage therefrom.

As mentioned above, the signal received by the receiving unit (4322) maybe passed to the signal conditioning unit (4324) and the ramping controlunit (4326). In the variation shown in FIG. 43, the signal conditioningunit (4324) may comprise a rectification unit (4334), an amplitudecontrol unit (4336), and a current source unit (4338). It should beappreciated that the signal conditioning unit (4324) may include onlysome of these individual components and/or may contain additionalcomponents as desired. In variations that include a rectification unit(4334), the rectification unit (4334) may be configured to convert anyalternating current signals to direct current signals. The rectifyingunit may be a half-wave rectifier or a full-wave rectifier, and in someinstances may be configured to smooth the rectified signal. For example,the variation of rectification unit (4334) shown in FIG. 43 may comprisea half-wave rectifier comprising a diode (4340) and a smoothingcapacitor (4342) placed at the output of the half-wave rectifier.

In variations that include an amplitude control unit (4336), theamplitude control unit (4336) may be configured to limit the maximumamplitude of the signal delivered by the output stage (4328). Forexample, the amplitude control unit (4336) shown in FIG. 43 may comprisea zener diode (4344), which may shunt current away from the signalconditioning unit (4324) when the voltage across the zener diode (4344)exceeds a threshold voltage. It should be appreciated that the amplitudecontrol unit (4336) may comprise any suitable current or voltagelimiting elements, which may be positioned in any suitable portion ofthe stimulator circuit (4300) (e.g., as part of the receiving unit(4322), the signal conditioning unit (4324), the ramping control unit(4326), the output unit (4328), combinations thereof, and the like). Insome variations, a stimulation circuit may comprise a plurality ofamplitude control units, each of which may limit a different aspect ofthe generated stimulation signal, or may limit aspects of the generatedcontrol signal at different locations.

In variations where the signal conditioning unit (4324) comprises acurrent source unit (4338), the current source unit (4338) may beconfigured to act as a voltage-controlled current source which mayoutput a current based on a voltage input received by the current sourceunit (4338). For example, in some variations (such as that shown in FIG.43), the current source unit (4338) may comprise a transistor (4346)(e.g., a JFET, MOSFET, BJT) where the gate and the source of thetransistor (4340) are connected (e.g., via a resistor (4348) or thelike). In some variations, the current source unit (4338) may act as aconstant-current source that may provide a constant current when anyvoltage above a certain threshold is applied to an input of the currentsource unit (4338). In some variations, a current source unit maycomprise one or more current-limiting diodes or the like. In somevariations the current source unit (4338) may comprise a current mirrorcircuit. The current mirror circuit may be symmetric or asymmetric.

Once the received output signal has been conditioned by the signalconditioning unit (4324), the signal may be passed to the output unit(4328). The output unit (4328) may thus deliver the processed signal asan output signal to tissue (4350) via electrodes (4352). In somevariations, the output unit (4328) may be configured to allow forpassive charge balancing. For example, output unit (4328) may comprise acapacitor (4354) and resistor (4356). The capacitor (4354) may chargewhen signal conditioning unit (4324) is delivering current to the outputunit (4328) and tissue (4350), and may discharge when the signalconditioning unit (4324) is not delivering current to the output unit(4328), which may allow the output unit (4328) to provide a biphasic,charge-balanced, stimulation signal to tissue (4350). In somevariations, the output unit (4328) may comprise a current-limitingdevice (not shown) or the like, which may limit the magnitude of thebalancing current produced by the capacitor (4354).

As mentioned above, the ramping control unit (4326) may be configured toramp the signal provided from the signal processing unit (4324) to theoutput unit (4326). As shown in FIG. 43, the ramping control unit (4326)may comprise a charging unit (4358) and a field-effect transistor(4360). The field-effect transistor (4360) may be any suitabletransistor (e.g., a MOSFET, BJT, or the like). The signal conditioningunit (4324) and the output unit (4328) may be connected to the sourceand drain terminals of the field-effect transistor (4360), and thecharging unit (4326) may be connected to the gate terminal of thefield-effect transistor (4360). As mentioned above, the current thatpasses between the signal conditioning unit (4324) and the output unit(4328) through the field-effect transistor (4360) may be dependent on avoltage provided by the charging unit (4326) to the gate terminal of thefield-effect transistor (4360). As such, the ramping control unit (4326)may be configured to increase the amplitude of the stimulation signal asthe charging unit (4326) charges.

Charging unit (4326) may be configured to increase the voltage providedto the field-effect transistor (4360) as the receiving unit (4322)receives an output signal generated by a controller. For example, asshown in FIG. 43, the charging unit (4326) may comprise a capacitor(4362) which may be charged as receiving unit (4322) receives the outputsignal. As the capacitor (4362) charges, the voltage applied to thefield-effect transistor (4360) may increase, which may thereby increasethe current that may pass from the signal conditioning unit (4324) tothe output unit (4328). This may result in a ramped stimulation signalproduced by the microstimulator. In some instances, the charging unit(4326) may comprise a rectifying diode (4364) or other rectificationcircuit which may rectify the signal received from the receiving unit(4322). Additionally, the charging unit (4326) may comprise one or moreadditional components (e.g., resistors (4366) and (4377), diode (4368)and transistor (4370), which may control the rate at which the capacitor(4362) charges and discharges. While the stimulator circuits describedabove with respect to FIGS. 36 and 43 are passive circuits thatpassively ramp a stimulation signal without the use of internal logic orintelligence, it should be appreciated that in some variations astimulation circuit as described here may comprise an microcontroller orother internal logic that may control the ramping of a stimulationsignal.

The microstimulators described above may take any of several shapes andforms. FIGS. 6A-6H illustrate exemplary microstimulators suitable foruse with the stimulation systems described here. It should beappreciated that each of the microstimulators shown in FIGS. 6A-6H mayinclude any of the circuitry or functionality described in more detailabove (e.g., a passive stimulation circuit), and may be hermeticallysealed. The microstimulators may comprise any suitable materials orcombinations of materials, such as, for example, one or more metals(titanium, niobium, stainless steels, platinum, alloys thereof,combinations thereof, or the like), one or more polymers, one or moreceramics, combinations thereof or the like. FIG. 6A depicts onevariation of a microstimulator (600) that is shaped like a capsule witha body and two ends. The body may be relatively straight with acylindrical, square, rectangular, trapezoidal or other shaped crosssection and rounded, pointed, or other shaped ends. The capsule-shapedmicrostimulator (600) may include electrodes (not shown) at one or moreends and/or along the length thereof, as will be described in moredetail below. The microstimulator may have any suitable dimensions. Forexample, in some variations, the length of the stimulator may be betweenabout 6 millimeters to about 30 millimeters. In some of thesevariations, the length of the stimulator may be about 16 millimeters. Insome variations, the height of the microstimulator may be between about0.5 millimeter and about 2 millimeters. In some of these variations, theheight of the microstimulator may be about 1.5 millimeters. In somevariations, the width of the microstimulator may be between about 3millimeters and about 10 millimeters. In some variations, the width ofthe microstimulator may be about 5 millimeters.

FIG. 6B depicts another variation of a microstimulator (602) that isshaped like a capsule having a curved body. In these variations, thecurvature of the body may be configured to accommodate an anatomicalstructure of a patient, such as a fossa for a lacrimal gland. It shouldbe appreciated that the body of the microstimulator (602) may have anysuitable ends and cross-sectional shape as described above in relationto the microstimulator (600) shown in FIG. 6A. Additionally, themicrostimulator (602) may comprise one or more electrodes (not shown),as will be described in more detail below.

While shown in FIG. 6B as having a single curve, it should beappreciated that the microstimulator (602) may comprise multiple curves.For example, FIG. 6C shows a microstimulator (604) comprising multiplecurves. As shown there, the microstimulator (604) includes a first curvein one direction and a second curve in a second direction. The curvesmay be formed in a single plane, as shown in FIG. 6C, or may be formedin different planes. Additionally, the microstimulator (604) may be aflexible device or may be configured to conform to an anatomicalstructure of a patient, such as a fossa for the lacrimal gland.

FIG. 6D depicts another variation of a microstimulator (606) that isconfigured as a planar structure. In some of these variations, themicrostimulator (606) may have a first form when it is being insertedinto a patient and manipulated to have a second form during or afterdelivery, as will be described in more detail below. The planarmicrostimulator (606) may be flexible and/or may be configured toconform to one or more anatomical structure, such as a fossa for alacrimal gland.

FIG. 6E illustrates a flexible segmented microstimulator (608) for usewith the stimulation systems described here. The flexible segmentedmicrostimulator (608) may include multiple electrodes (610) separated bybody segments (612). The electrodes may be implemented as part of astimulation circuit for stimulating one or more anatomical targets suchas a lacrimal gland. While the microstimulator (608) is shown in FIG. 6Eas forming a single curved such that the electrodes (610) are alignedalong the curve, it should be appreciated that the microstimulator neednot form a single curve. For example, FIG. 6F shows a variation of aflexible segmented microstimulator (614) comprising a plurality ofelectrodes (616) connected by body segments (618) such that electrodes(616) extend approximately parallel to other electrodes (616).

FIGS. 6G and 6H illustrate one variation of a microstimulator (620) thatis incorporated into a contact lens (622). As shown there, the contactlens (622) may be positioned over an iris (626) of an eye (630) and maycomprise one or more electrodes (628). The contact lens (622) may be incontact with the cornea, and its inner surface may conform to the shapeof the cornea and/or the conjunctiva. The microstimulator (620) maycontain any suitable number of electrodes (628) (e.g., one, two, orthree or more electrodes), and may deliver an electrical current to thesurface of the eye, which may result in reflex activation.

In some variations, the contact lens (622) may have a power supply(e.g., a battery or the like). Additionally or alternatively, thecontact lens (622) may comprise one or more coils (624) or otherelements which may receive energy from a controller. FIG. 6H is anenlarged view of the coils (624) shown in FIG. 6G. The microstimulator(620) may be powered in any suitable manner, such as by one or more ofthe controllers as described below. In some variations, themicrostimulator (620) may be powered by a magnet placed within theeyelids. In some variations, the microstimulator may be activated byblinking an eye, in which case a blink detection mechanism may be usedin conjunction with the microstimulator.

As mentioned above, the microstimulators described here may comprise oneor more electrodes. The electrodes may be attached to any suitableportion or portions of the microstimulator, and in some instances may beconnected to the microstimulator via one or more leads. In somevariations, the electrodes may be configured to allow for capacitivecharge transfer, but not faradaic charge transfer. When themicrostimulator comprises a planar body, such as the microstimulator(606) described above with respect to FIG. 6D, the microstimulator mayinclude electrodes on both sides of the planar structure, or may onlyinclude electrodes on one side of the planar structure. Themicrostimulators may comprise any suitable number of electrodes (e.g.,one, two, three, or four or more electrodes). FIGS. 7A-7F depictillustrative microstimulators having different electrode configurations.For example, FIG. 7A illustrates a microstimulator (700) including astimulation circuit (702) with electrodes (704) coupled thereto. Itshould be appreciated that the stimulation circuit (702) shown in FIG.7A may be any suitable stimulation circuit, such as one or more of thestimulation circuits described in more detail above. Electrodes (704)may be coupled to the stimulation circuit (702) at the ends of themicrostimulator (700), as shown in FIG. 7A, or may be connected alongthe body of the microstimulator (700).

FIG. 7B shows another variation of a microstimulator (706) whichincludes electrodes (708) that are attached to the microstimulator (706)via small round contact points on the exterior of the microstimulator(706). While shown in FIG. 7B as being attached to the ends of themicrostimulator (706), one or more of the electrodes may be attachedalong the body of the microstimulator (706). In other variations, theelectrodes may be at least partially embedded or nestled into a surfaceof the microstimulator. For example, FIG. 7C illustrates amicrostimulator (708) having nestled electrodes (710). While theelectrodes (710) are shown in FIG. 7C as being configured as a circularpattern, it should be appreciated that a nestled electrode (710) mayhave any suitable shape and/or pattern.

In some variations, one or more electrodes may be attached to amicrostimulator via one or more leads. The leads may or may not beflexible or comprise one or more flexible portions. For example, FIG. 7Ddepicts one variation of a microstimulator (712) comprising electrodes(714) attached to the microstimulator (712) via flexible leads (716).The flexible leads (716) may be manipulated into one or more shapes totraverse through one or more regions of the body and/or conform thereto.FIG. 7E shows another variation of a microstimulator (718) that includeselectrodes (720) attached to the microstimulator (718) via rigid leads(722). It should be appreciated that in variations where amicrostimulator comprises a lead, the microstimulator may comprise anysuitable number of leads (e.g., one, two, three, or four or more leads),and each lead may include any suitable number of electrodes (e.g., one,two, three, or four or more electrodes).

In variations where a microstimulator includes electrodes attached tothe body of the microstimulator via one or more leads, the leads mayallow for the body of the microstimulator to be located remotely fromthe site of stimulation. For example, FIG. 7F shows one variation of animplanted microstimulator (723) comprising a body (724) and a pluralityof electrodes (728) attached to the body (724) via a lead (726). Asshown there, the electrodes (728) may be configured to deliver astimulation signal (730) to tissue around the eye (e.g., the lacrimalgland), but the body (724) (which may include one or more stimulationcircuits) may be remotely positioned (e.g., behind the ear as shown inFIG. 7F, or at another location in the head, neck, or torso).

As mentioned above, a microstimulator may be configured to change shapeupon implantation from a delivery device. For example, FIGS. 8A and 8Bdepict one variation of a microstimulator (800) that is configured tochange shape upon implantation from a delivery device (802) (e.g., aneedle or the like). Specifically, the microstimulator (800) may have afirst low-profile form when placed inside of a delivery device. Themicrostimulator (800) may be rolled, crimped, folded or otherwisemanipulated to achieve this low-profile form. For example, in FIG. 8A,the microstimulator (800) is shown as being folded into the firstlow-profile form.

When the microstimulator (800) is released from the delivery device(802) (e.g., via a pusher or the like), the microstimulator (800) maytake on a second form. When in its second form, the microstimulator(800) may conform to one or more anatomical structures, such as a fossafor the lacrimal gland. The microstimulator (800) may transition betweenthe first and second forms in any suitable manner. For example, in somevariations the microstimulator (800) may unfold, unfurl, or otherwisechange shape due to release of stored energy in the microstimulator(800) (e.g., shape memory energy, spring or coil energy, or the like).In other instances, the microstimulator (800) may change shape due tomechanical manipulation, or by virtue of degradation or other removal ofa structure holding the microstimulator (800) in the low-profile form.

In some variations, the microstimulators may comprise one or morecomponents which may aid in insertion of the device into tissue. Forexample, in some variations a microstimulator may comprise one or morerounded edges which may reduce tissue damage as the microstimulator isadvanced into or past tissue. Additionally or alternatively, amicrostimulator may comprise one or more sharpened tips which may aid inadvancing the microstimulator at least partially into or through tissue.For example, FIGS. 9A and 9B show one such variation of amicrostimulator (900). As shown in FIG. 9A, the microstimulator (900)may comprise a beveled tip (902). In some instances, the microstimulator(900) may be advanced using a delivery device (904), as shown in FIG.9B, and the narrowed edge (906) of the beveled tip (902) may cut orotherwise separate tissue as the microstimulator (900) is advanced usingthe delivery device (904). While shown in FIG. 9A as being beveled, thetip of a microstimulator may be pointed or otherwise sharpened. Itshould also be appreciated that the sharpened tip may comprise one ormore barbs, as will be described in more detail below, which may help toprevent migration after delivery of the microstimulator.

FIG. 10 shows another variation of a microstimulator (1000) whichcomprises a helical barb (1002) extending therefrom. The helical barb(1002) may be configured such that the microstimulator (1000) may berotated during delivery to screw the helical barb (1002) into tissue.This may assist in advancing the microstimulator, and also may anchorthe microstimulator in place relative to tissue.

In variations where a microstimulator comprises a sharpened tip, the tipmay be formed as a single device or may be formed separately from andattached to the microstimulator. In some variations, the tip may beconfigured to degrade or otherwise detach from the microstimulator afterimplantation. For example, FIGS. 11A and 11B show one such variation ofa microstimulator (1100). As shown in FIG. 11A, microstimulator (1100)may comprise a body (1102) and a biodegradable pointed tip (1104). Thepointed tip (1104) may aid in delivery of the microstimulator (1100) bypuncturing or otherwise separating tissue during advancement of themicrostimulator (1100). Once in place in the body, the tip (1104) maybiodegrade such that the body (1102) of the microstimulator (1100) isleft in place, such as shown in FIG. 11B. The biodegradable tip may bemade from any suitable biocompatible, biodegradable material ormaterials, such as one or more biodegradable sugars or polymers (e.g.,PLA, PLGA, or the like).

The microstimulators described here may also comprise one or moreelements which may help to maintain the microstimulator in placerelative to tissue. In some variations, the microstimulator may compriseone or more coatings (e.g., an adhesive coating or the like) which mayhelp hold in the microstimulator in place relative to tissue. In othervariations, the microstimulator may comprise one or more materials(e.g., a Dacron covering) or structures that may promote tissueingrowth. In some variations, the microstimulator may comprise one ormore fixation elements, such as hooks, barbs, anchors, bumps, or otherprotrusions. For example, FIG. 12 illustrates a microstimulator (1200)having a plurality of barbed fixation elements (1202). While thefixation elements (1202) are shown in FIG. 12 as being attached to thebody of the microstimulator, it should be appreciated that fixationelements may be affixed to any suitable portion of the microstimulator.In variations where the microstimulator comprises a sharpened tip, thetip may comprise one or more fixation elements. In variations where themicrostimulator comprises one or more leads, one or more of the leadsmay comprise one or more fixation elements. For example, FIG. 13 depictsanother variation of a microstimulator (1300) which comprises leads(1302) having barbed fixation elements (1304) located thereon. It shouldbe appreciated that the leads may comprise any suitable fixationelement, such as those described immediately above.

It should be appreciated that a microstimulator may comprise a pluralityof different fixation elements. For example, FIG. 14 illustrates avariation of a microstimulator (1400) comprising a plurality of bumps(1402) and ring members (1404) protruding from the microstimulator(1400). In these variations, the bumps (1402) and the ring members(1404) may resist movement of the microstimulator (1400) relative totissue. Additionally, the ring members (1404) may promote tissueingrowth which may further help hold microstimulator (1400) in placerelative to tissue. Additionally or alternatively, one or more sutures(not shown) may be threaded through the ring members to help sew thedevice in place relative to tissue. The microstimulator may comprise anysuitable combination of fixation elements as described above.

In some variations of the microstimulators described here, themicrostimulator may comprise one or more features to facilitateminimally invasive retrieval. For example, FIGS. 15A-15C depictillustrative variations of microstimulators that include retrievalfeatures. 15A shows a variation of a microstimulator (1500) comprising arecapture loop (1502). The recapture loop (1502) may comprise anaperture (1504), and may aid in retrieval of the microstimulator (1500).Specifically, during retrieval, a physician may use a retrieval devicesuch as forceps or a hook device to engage recapture loop (1502) andremove the microstimulator (1500) from its position within the body. Insome variations, a suture (not shown) may be attached to the recaptureloop (1502), and the suture may be engaged by a physician (e.g., via aretrieval device) to pull the microstimulator (1500) from its position.A microstimulator may or may not comprise multiple recapture loops(1502), and these recapture loops may be located at one or both ends ofthe microstimulator (1500), and/or along the length of the body of themicrostimulator (1500). While the microstimulator is shown in FIG. 15Aas having a capsule-shaped body similar to the microstimulator (600)described above with respect to FIG. 6A, it should be appreciated thatany microstimulator described here may comprise a recapture loop.

FIG. 15B illustrates another variation of a microstimulator (1510)having a recapture magnet (1512). Recapture magnet (1512) may be engagedby another magnetic device to assist in removal or repositioning of themicrostimulator (1510). It should also be appreciated that the recapturemagnet (1512) may also be engaged by a delivery device and may assist inpositioning the microstimulator (1510) during delivery.

FIG. 15C illustrates another variation of a microstimulator (1520)having a shaped retrieval tab (1522). Also shown there is a retrievaldevice (1524) having an aperture (1526) at a distal end thereof. To aidin retrieval of the microstimulator (1520), the retrieval device (1524)may be advanced so that the aperture (1526) receives a portion of theretrieval tab (1522) in the aperture (1526), and may be rotated totemporarily connect the microstimulator (1520) and the retrieval device(1524). Once connected, the retrieval device (1524) may be manipulatedor withdrawn to reposition or remove the microstimulator.

FIGS. 42A-42C illustrate another variation of a microstimulator (4200)described here. Specifically, FIG. 42A shows a perspective view of themicrostimulator (4200). As shown there, the microstimulator (4200) maycomprise a housing (4202) and a flexible extension (4204) connected tothe housing (4202). The housing (4202) may be hermetically sealed, andmay contain some or all of the stimulation circuitry therein. Themicrostimulator (4200) may comprise any stimulation circuits, such asthose described above. The housing (4202) may be formed from one or moremetals (e.g., titanium) or other biocompatible materials.

The extension (4204) may be formed from a flexible material such assilicon, and may comprise a first electrode (4206), a second electrode(4208), and a coil (4210). In some variations, the extension (4204) maybe a molded component, such as molded silicon. The flexible extension(4204) may conform to one or more portions of the anatomy (e.g., theorbit or the lacrimal gland) when implanted in tissue. FIG. 42B shows aside view of the microstimulator (4200). As shown there, the thicknessof the extension (4204) may be less than that of the housing (4202), andmay taper to the thickness of housing (4202). It should be appreciatedthat in some variations the thickness of the extension (4204) may be thesame as or greater than the thickness of the housing (4202).Additionally, the width of the extension (4204) is shown in FIG. 42A asbeing greater than the width of the housing (4202), and may taper to thethickness of the housing (4202). In some variations, however, thehousing may have the same width, or may be wider than the extension.

While shown in FIG. 42A as having two electrodes, it should beappreciated that the microstimulator (4200) may comprise any suitablenumber of electrodes (e.g., one, two, three, or four or moreelectrodes). Some or all of the electrodes may be textured or patterned,which may enhance the effective surface area of the electrodes. One ormore of the electrodes may be recessed, which may provide for moreuniform charge density on the electrode surface. In the variation shownin FIG. 42A, the first electrode (4206) and second electrode (4208) arepositioned on the same side of the extension (4204), although in somevariations the first (4206) and second (4208) electrodes may bepositioned on opposite sides of the extension (4204). Additionally,while shown in FIG. 42A as having a coil (4210), it should beappreciated that the microstimulator (4200) may comprise any energyreceiving element or elements as described in more detail below.

The electrodes (4206) and (4208) and coil (4210) may be connected to themicrostimulator circuitry via one or more feedthroughs. For example,FIG. 42C shows a perspective view of the housing (4202) with theextension (4204) removed. As shown there, housing (4202) may comprise aplurality of feedthroughs (4212) that extend through the housing (4202).One or more elements (e.g., one of the electrodes (4206) or (4208) orthe coil (4210)) may be electrically connected to thehermetically-sealed stimulation circuitry by connection to thefeedthroughs (4212). Additionally, some of the feedthroughs (4212) maycomprise an insulating member (4214) which may electrically isolate thefeedthrough (4212) from the housing (4202).

The microstimulators described here may be made from any materials orcombinations of materials. For example, the composition of the electrodemay include, but is not limited to, platinum, iridium, platinum iridium,iridium oxide, sputtered iridium oxide, titanium nitride, tantalum, andcombinations thereof. In some variations, the implantablemicrostimulators described here may be configured to be compatible withmagnetic resonance imaging (MRI) machines. In some of these variations,the device may be configured to minimize device movement that may resultfrom magnetic forces created during MRI imaging or minimize heating thatmay occur in the components of the microstimulator. For example, in somevariations, the microstimulator may be made from non-ferromagnetic orreduced-ferromagnetic materials. In other variations, themicrostimulator may comprise ferromagnetic materials, but the relativeamount of these components may be small enough such that forces providedon these components during MRI imaging do not substantially move thedevice. In other variations, the microstimulators may be configured suchthat MRI imaging does not cause inadvertent stimulation or otheractivation of the microstimulator. For example, when themicrostimulators comprise a receiving circuit having a resonantfrequency (as discussed in more detail above), the microstimulator maybe configured such that the resonant frequency is outside of thefrequency ranges produced during MRI imaging (e.g., the frequenciesproduced by the main field, gradient field, and/or RF fields of an MRIscanner).

In some variations, the microstimulator may comprise one or more sensorswhich may measure one or more physical parameters of the patient. Insome variations, the sensors may be used to implement closed loopstimulation of one or more anatomical structures. FIG. 37 illustrates amicrostimulator implemented with closed loop control of lacrimalstimulation. As shown there, a microstimulator (3706) may includesensors (3708) and an electrode-bearing lead (3704). The sensors (3708)may be positioned on the patient's eyeball, and the lead (3704) mayextend between microstimulator (3706) and one or more anatomicaltargets, such as a lacrimal gland (3710). The microstimulator (3706) maybe configured to stimulate the anatomical targets via lead (3704) basedon closed-loop stimulation using signals measured by the sensors (3708).When stimulated by one or more signals, tears may be produced under theupper eye lid (3720) and may travel over an iris (3700) of the patient'seye assembly. In variations where the microstimulator comprises asensor, the microstimulator may be configured to transmit informationreceived from the sensor to a controller.

Closed loop stimulation may work by detecting a condition (surfaceimpedance to detect wetness) that provides information about therequirement of tear production and generating a condition signal. Themicrostimulator (or controller) may then modulate its output in responseto this condition signal to modify its output in tear production.Detecting the condition may include measurement of one or morevariables. Measured variables for use in the closed loop stimulation mayinclude one or more of tear conductivity, tear volume, and glandconductivity. A sensing element may be part of an implantable microstimulator, or could be separate (e.g., provided in a contact lens, partof the controller, etc.) from the implanted microstimulator. Theadjustment of stimulation output may be based on an algorithm.

Controller

As mentioned above, the stimulation systems described here may comprisea controller, which may communicate with the stimulation devicesdescribed here to transmit and/or receive power, information, or thelike. The components of the controller and the microstimulator may beimplemented as a single device or as separate devices. The controllermay communicate with the microstimulator wirelessly and/or via a wiredconnection. The controller may be configured for implantation within thebody, or may be configured to remain external to the body. Thecontroller may be disposable, may be reusable, or may be partiallyreusable. In some instances, one or more components of themicrostimulator may be reusable, while other components may bedisposable. In some instances, the controller may be rechargeable.

When the controller is configured to remain external to the body, thecontroller may be configured to be at least temporarily affixed to thepatient. For example, the controller may be configured to adhesivelyaffix to the patient's skin, may be magnetically attached to a patient'sskin (e.g., via one or more magnets positioned in the patient's head),may be incorporated into a pair of eyeglasses, may be configured to beworn over or otherwise attach to the ear, may be incorporated into orotherwise couple to a wrist-watch or bracelet, or the like. Thecontroller may be configured for placement against any suitable skinsurface, such as the temple, forehead, brow, ear, neck, or the like, asmay be appropriate to position a controller in proximity to an implantedstimulator. In other variations, the controller may comprise one or morehand-held devices, such as a key fob.

In some variations, the controller may comprise a patch or similarstructure which may be configured to at least temporarily affix thecontroller to a patient. FIG. 16A shows one such variation of astimulation system (1600) which includes a controller (1602) configuredto adhesively affix to the skin (1604) of a patient (1606). As shownthere, the controller (1600) may comprise a patch (1608) with one ormore adhesive layers (not shown) which may temporarily connect the patch(1608) to the patient (1606). The controller (1602) may communicate witha microstimulator (1610) via a wireless signal (1612), as described inmore detail below. The microstimulator (1610) may in turn provide anoutput signal (1614) for stimulating one or more anatomical targets of apatient, as described hereinthroughout.

FIG. 16B shows a cross-sectional side view of one variation of acontroller (1620) which comprises a patch (1622). As shown there, thepatch (1622) may comprise a base layer (1624), controller circuitry(1626), a coating layer (1628), an adhesive layer (1630), and a releaseliner (1632). The release liner (1632) may be peeled off or otherwiseremoved from adhesive layer (1630), and the patch (1622) may be placedagainst a surface (e.g., the skin of a user) to temporarily affix thepatch (1622) thereto via the adhesive layer (1630).

While the controller circuitry (1626) is shown in FIG. 16B as beingseparate from base layer (1624) and coating layer (1628), it should beappreciated that the circuitry of a controller may be incorporated intoany portion of the patch. For example, in some instances at least someof the controller circuitry may be incorporated into one or more layersof the patch (e.g., a base layer, coating layer, adhesive layer,combinations thereof, or the like). In variations where a patchcomprises a base layer, the base layer (or one of the other patchlayers) may include one or pads or fabric layers, which may provideadditional comfort to a patient when a controller is attached thereto.Additionally or alternatively, the base layer may comprise a printedcircuit board which incorporates one or more components of thecontroller circuitry.

While the patch (1622) is shown in FIG. 16B as having a coating layer(1628), it should be appreciated that a patch need not have any coatinglayer, or may be have multiple coating layers. In variations where apatch comprises one or more coating layers, the coating layers mayprovide one or more useful functions. In some instances, a coating layermay comprise a material (which may be a soft durometer material) such assilicone, latex, parylene, one or more plastics, etc., and may beconfigured to protect one or more device components, such as thecontroller circuitry. The coating layer may, in some instances, beconfigured to provide additional comfort to a patient. In somevariations, the coating layer may be configured to prevent accidentalremoval of the patch. Additionally or alternatively, the patch maycomprise an insulating coating layer (e.g., a layer made from latex,parylene, or the like), which may help maintain hermeticity of the patchand/or insulate a patient from voltages generate within the device.Additionally or alternatively, the patch may comprise a layer which mayintensify or direct a magnetic field produced by the controller, and/ormay reduce eddy current loss. These layers may comprise one or moreferrites, patterned ferrites, or the like.

In some variations, a coating layer may be disposed between differentcomponents of the controller circuitry. For example, FIG. 44 shows anexploded view one such variation of a patch (4400). As shown there,patch (4400) may comprise a circuit board (4402), a reflective layer(4404), and a coil (4406). The reflective layer (4404) may be positionedbetween the circuit board (4402) and the coil (4406), and may beconfigured to shield the components of the circuit board (4402) from amagnetic field created by the coil (4406) during generation of an outputsignal. For example, the reflective layer (4404) may minimize eddycurrents that may be created in circuit components of the circuit board(4402). Additionally, the reflective layer (4404) may shape or otherwisedirect the generated magnetic field away from the reflective layer(4404), which may increase the power transmission to an implantedmicrostimulator. The patch (4400) may comprise one or more adhesivelayers or other layers as discussed in more detail hereinthroughout.

It should be appreciated that one or more of the patch components may beflexible and/or may be configured to at least partially conform to thecontours of the patient. For example, the circuitry of the controllermay be incorporated into a flexible substrate or layer (e.g., a flexiblecircuit board). In variations where a patch comprises one or more padsor fabric layers, these layers may be flexible. The patch may also beformed from one or more translucent materials, or may be colored tomatch a patient's skin tone, which may make the patch less noticeable.

As discussed above, the patch may comprise one or more adhesive layersfor affixing the controller to a surface. In some variations, theadhesive layer may comprise a double-sided adhesive, in which one sideof the adhesive adheres to one or more patch components (e.g., a fabriclayer, printed circuit board, or the like) and the other side of theadhesive adheres to the skin. An adhesive layer may be configured tolast any suitable amount of time. In some variations, the adhesive layermay be configured to last for one or more hours (e.g., one hour, fourhours, eight hours, or the like), one or more days (e.g., one day, twodays, three days, etc.), or one or more weeks (e.g., one week, twoweeks, etc.). The patches described here may further comprise a releaseliner, but need not. In variations that do comprise a release liner, therelease liner may comprise a wax-coated paper or other material thattemporarily covers an adhesive layer. The release liner may be peeledoff or otherwise removed to expose a surface of the adhesive layer,thereby allowing the adhesive layer to be placed against skin or anotherdesired surface. In some variations, the controller may be configuredsuch that removal of a release liner activates one or more functions ofthe device. For example, in some variations, removal of a release linermay initiate the generation of a timed output signal, as will bedescribed in some detail below.

As mentioned above, in some variations a patch may comprise multipleadhesive layers. FIG. 16C shows on such example of a controller (1640)comprising a patch (1642) having a first adhesive layer (1644) and asecond adhesive layer (1646). Also shown there is a first release liner(1648) positioned between the first and second adhesive layers, and asecond release liner (1650) covering the second adhesive layer (1646).In these variations, the different adhesive layers may be used to attachthe patch (1642) to a patient during different time periods. Forexample, the second release liner (1650) may be removed to expose secondadhesive layer (1646), and the controller may be attached to a patientor other surface via the second adhesive layer (1646) for a first periodof time. After this period of time, the first release liner (1648) maybe removed to remove what may remain of the second adhesive layer (1646)and to expose the first adhesive layer (1644). The controller may thenbe reattached to the patient or other surface via the first adhesivelayer (1644). In this way, multiple adhesive layers may allow forcontinued use of a controller, even after one or more of the adhesivelayers have already been used. For example, in some variations acontroller may comprise a plurality of adhesive layers separated byrespective release liners. The patient may remove a release liner anduse the exposed adhesive layer to attach the controller to the patientfor one treatment period (e.g., at night while the patient sleeps). Thecontroller may be removed following the treatment period, and a newadhesive layer may be utilized each time the patient wishes to reattachthe controller. In some instances, one or more portions of the releaseliner may be labeled to indicate which day of the week a specificadhesive layer should be removed.

It should be appreciated that in variations where a patch comprisesmultiple adhesive layers, each adhesive layer may comprise the sameadhesive, or different layers may comprise different adhesives.Additionally or alternatively, each of the adhesive layers may beconfigured to last the same amount of time, or different adhesive layersmay be configured to last for different amounts of time. Additionally,when a controller comprises multiple release liners covering multipleadhesive layers, it should be appreciated that removal of some or all ofthe release liners may activate one or more functions of the controller.In some of these variations, removal of each release liner may activatea function of the controller. For example, removal of a first releaseliner may initiate the generation of a first timed output signal, andremoval of a second release liner may initiate the generation of asecond timed output signal. In other variations, removal of some releaseliners may activate one or more controller functions, while removal ofother release liners does not alter the controller function. Forexample, in some variations, removal of a first release liner mayinitiate the generation a first timed output signal, but removal ofsubsequent release liners does not affect operation of the controller.

In some variations of the stimulation systems described here, acontroller may be incorporated into a pair of eyeglasses. FIGS. 17A and17B illustrate two such variations of controllers for use with thestimulation systems described here. FIG. 17A shows a stimulation system(1700) which includes a controller (1702) which is embedded within theframe of a pair of eyeglasses (1704). The controller (1702) may generatean output signal (1706) which may be received by an implantedmicrostimulator (1708). The implanted microstimulator (1708) maygenerate a stimulation signal (1710) used to stimulate an anatomicaltarget, as described in more detail below. The controller (1702) may beembedded into any suitable portion of the eyeglasses (e.g., the frame, anose piece, etc.).

While the controller (1702) shown in FIG. 17A is embedded within a pairof eyeglasses (1704), it should be appreciated that in some instances acontroller may be attached to a pair of eyeglasses. For example, FIG.17B shows another variation of a stimulation system (1720) comprising acontroller (1722) which is attached to the frame of a pair of eyeglasses(1724). Controller (1722) may be temporarily or permanently attached toeyeglasses (1724), and may be attached in any suitable manner. In somevariations, the controller (1722) may be attached to the pair ofeyeglasses (1724) via one or more adhesives. In other variations, thecontroller (1722) may be configured to clip to or otherwise mechanicallyconnect to the eyeglasses (1724). In some instances, the controller(1722) may be configured to slide over one or more portions of theeyeglasses (1724) In instances where a controller is releasably attachedto a pair of eyeglasses, the controller can be replaced without needingto replace components of the eyeglass (1724). Additionally, if a patientwishes to switch between different pairs of eyeglasses (e.g., betweenun-tinted lenses and sunglasses), a releasably-attachable controller maybe switched between the different eyeglasses. The controller (1722) maygenerate an output signal (1726), which may be received by an implantedmicrostimulator (1728). The implanted microstimulator (1728) maygenerate a stimulation signal (1730) which may be used to stimulate ananatomical target, as described in more detail below.

In other variations, a controller may be incorporated into a devicewhich may be worn over or behind the ear of a user. For example, FIG. 18shows one such example of a stimulation system (1800) comprising acontroller (1802) which may be worn over the patient's ear near themastoid region (1804) of the temporal bone. In some instances, thecontroller (1802) may comprise one or more adhesives to help hold thecontroller (1802) in place relative to the ear. The controller (1802)may generate an output signal (1806) which may be received by animplanted microstimulator (1808). The implanted microstimulator (1808)may generate a stimulation signal (1810) used to stimulate an anatomicaltarget, as described in more detail below.

In still other variations, the controller may be attached to a portionof the ear itself. For example, FIG. 19 shows one such variation of astimulation system (1900) that includes a controller (1902) comprisingan earring (1904) which may be attached to the ear of a patient. Thecontroller (1902) may generate an output signal (not shown) received bya portion of an implanted microstimulator (1906). The implantedmicrostimulator (1906) may generate a stimulation signal (1908) used tostimulate an anatomical target, such as the microstimulator (723)described above with respect to FIG. 7F.

In some variations, a controller may be configured for placement in theformix of an eye under the eyelid. For example, FIG. 20 shows onevariation of a stimulation system (2000) that includes a microstimulator(2002) and an implantable microstimulator (2004) and a controller (2006)placed in the formix under the upper eyelid (2008) of a patient. Thecontroller (2006) may be flexible and/or conformable, and may be shapedto match or accommodate the curvature of the eyeball and/or formix. Insome variations, the controller (2006) may be rechargeable. In somevariations, the controller (2006) may be disposable. While themicrostimulator (2002) is shown in FIG. 20 as being positioned on thelacrimal gland (2010), it should be appreciated that a formix-basedcontroller may be used with a microstimulator positioned in any suitablelocation. In some variations, a formix-based controller may be attachedto or incorporated into a contact lens which may be worn by the patient.It should also be appreciated that one or more microstimulators may beconfigured for placement in the formix.

FIG. 21 depicts another exemplary external controller for use with thestimulation systems described here. As shown there, a stimulation system(2100) includes a controller (2102) comprising a hand-held device(2104). The controller (2102) may be brought to the vicinity of animplanted microstimulator (2106), and may produce an output signal(2108) received by the implanted microstimulator (2106). The implantedmicrostimulator may in turn generate a stimulation signal (2110) used tostimulate an anatomical target, as described in more detail below. Thehand-held device may be configured as a key fob, a wrist watch, oranother suitable structure.

As mentioned above, some variations of the stimulation systems describedhere may comprise an implantable controller. For example, FIG. 22depicts one variation of a stimulation system (2200) comprising animplantable controller (2202) and an implantable microstimulator (2204).Implantable controller (2202) may produce an output signal (2206), whichmay be received by the implantable microstimulator (2204). Theimplantable microstimulator (2204) may in turn generate a stimulationsignal (2208) used to stimulate an anatomical target. In instances wherethe implantable microstimulator (2204) is implanted in a target locationwhere space is limited, a remotely positioned implantable controller(2202) may allow for circuitry or other components to be implanted in apatient without having to be positioned at the target location. Whilethe implantable controller (2202) is shown in FIG. 22 as being implantedin the head of a patient, it should be appreciated that the implantablecontroller (2202) may in any suitable location of the body (e.g., thehead, neck, torso, or the like). It should be appreciated that ininstances where a stimulation system (2200) comprises an implantablecontroller (2202), the stimulation system (2200) may comprise one ormore external devices (such as one or more of the controllers describedabove) which may be configured to provide programming instructions tothe implantable controller (2202) and/or may recharge the implantedcontroller (2202) in variations where the implanted controller (2202)comprises a rechargeable power source.

In still other variations, some or all of the controller components maybe incorporated into an implantable stimulation device. For example, insome variations a stimulation device may comprise an implantable pulsegenerator with an internal power source. FIG. 23A depicts one variationof a stimulation system (2300) comprising an implantable microstimulator(2302). As shown there, the implantable microstimulator (2302) maycomprise a pulse generator (2304) connected to a lead (2306) thatcomprises a plurality of electrodes (2308). The lead (2306) may bepositioned such that the electrodes (2308) may be positioned adjacent toor in the lacrimal gland (2310), although it should be appreciated thatthe electrodes (2308) may be positioned near any suitable tissue asdescribed in more detail below. The pulse generator (2304) may compriseone or more batteries or other power sources, and may be configured toproduce one or more stimulation pulses or other signals that are appliedto the electrodes to stimulate one or more desired anatomical targets.While shown in FIG. 23A as comprising a multi-electrode lead (2306), insome variations the stimulation device may comprise one or moremonopolar electrode leads.

When an implantable stimulation device comprises an implantable pulsegenerator with an internal power source, the pulse generator may beimplanted in any suitable location in the body. For example, FIG. 23Bshows the stimulation system (2300) with the pulse generator (2304)implanted near a patient's clavicle bone. The lead (2306) may extendwithin the body of the patient from the pulse generator (2304) to atarget location (e.g., the lacrimal gland). In other variations, thepulse generator (2304) may be positioned in the head or neck. It shouldbe appreciated that in instances where a microstimulator (2302)comprises an implanted pulse generator (2304), the stimulation system(2300) may still comprise one or more external devices (such as thosedescribed above) which may be configured to provide programminginstructions to the pulse generator (2304) and/or may recharge the pulsegenerator (2304) in variations where the microstimulator (2302)comprises a rechargeable power source.

As mentioned above, the controller may be configured to transmit one ormore signals to an implanted microstimulator. In some variations, theoutput signal produced by the controller may provide power to themicrostimulator. For example, in variations in which a stimulationsystem comprises a microstimulator having a passive stimulation circuit(or a stimulation circuit that does not otherwise include a battery orinternal power supply), the controller signal may power the stimulationdevice. In variations in which a microstimulator of a stimulation systemcomprises a power source, the signal of the controller may temporarilyprovide power to the microstimulator to assist in microstimulatoroperation and/or to recharge the power supply of the microstimulator. Invariations where a stimulation system comprises an implanted controller,an external controller may provide a signal to recharge or otherwisepower the implanted controller.

In some variations, one or more of the signals produced by thecontroller may transmit information to one or more portions of thestimulation system. For example, in variations where a stimulationsystem comprises a microstimulator having an implantable pulsegenerator, the controller may provide programming instructions (e.g.,stimulation parameters, stimulation times, etc.) to the implantablepulse generator. Similarly, in variations where a stimulation systemcomprises an in implanted controller, an external controller may beconfigured to provide one or more control signals or other informationto the implanted controller. In variations where a microstimulatorcomprises an adjustable component, one or more output signals of thecontroller may be used to adjust the adjustable component.

FIG. 30 depicts a schematic diagram of one variation of a controller(3000) circuit suitable for use with the stimulation systems describedhere. As shown there, the controller (3000) may include a power source(3002), an input module (3004), a controller (3006), and a transmissioncomponent (3008). The power source (3002) may provide a voltage orcurrent to the controller (3006). The supplied power may be a constantvoltage or current or an alternating voltage or current.

Input module (3004) may provide one or more inputs signals to controller(3006) based on input received from a user such as a patient, a healthprofessional, or other external source. For example, the user input maybe a depressed button, an input along a slide bar, or some other inputthat indicates whether to apply stimulation to one or more anatomicaltargets (such as a lacrimal gland), what type of stimulation to apply,and/or what stimulation parameters to apply. The input signals may alsobe generated from logic inside the input module (3004). For example,input module (3004) may include logic to apply stimulation to a lacrimalgland periodically, in a ramped fashion, continuously, in a patternedfashion, in response to detecting a condition of low or decreased tearproduction, or some other condition. In some variations the stimulationmay be ramped to prevent activation of pain sensation.

Controller (3006) may receive power from power source (3002) and inputsignals from input module (3004) to generate an output signal. Theoutput signal may be a voltage signal or a current signal applied totransmission element (3008). The output signal may vary in frequency,amplitude, period and/or phase based on the input received from inputmodule (3004) and power received from controller (3002). Thetransmission element (3008) may be any element suitable for conveyingenergy and/or information to a microstimulator (not shown), such as oneor more coils, ultrasound generators, optical energy generators, or thelike. When the output signal is applied to a transmission element (3008)including a coil, the coil may generate a magnetic wave having a radiofrequency and amplitude based on the output signal and coil. In somevariations, the controller (3006) may detect one or more operatingparameters of the microstimulator.

While the controller (3006) is shown in FIG. 30 as having an inputportion, it should be appreciated that the controller need not have aninput portion. FIG. 45A depicts a block diagram of another variationcontroller circuit (4500) comprising a power source (4502), a controller(4504), and a transmission portion (4506). As described in more detailabove, the power source (4502) may provide power to the controller(4504). The controller (4504) may be programmed or otherwise configuredto produce one or more output signals, which may be transmitted to amicrostimulator via transmission portion (4506).

FIG. 45B depicts one variation of a controller circuit (4510) comprisinga power source (4512), a controller (4514), and a transmission portion(4516) as described immediately above. As shown there, the power source(4512) may comprise a battery (4518) in parallel with a capacitor(4520), although it should be appreciated that the power source (4512)may include any suitable elements. In this variation, the battery (4518)may continuously charge the capacitor (4520), and the capacitor (4520)may provide current to the controller (4514) during generation of anoutput signal when the electrochemical reactions of the battery (4518)is not fast enough to provide the amount of current required to generatethe output signal. The power source (4512) may or may not berechargeable.

The power source (4512) may provide power to the controller (4514),which may generate an output signal. In the variation shown in FIG. 45B,the controller may comprise a pulse generator (4522), a first transistor(4526) and a second transistor (4524). The pulse generator (4522) may beconnected to the first and second transistors such that current may flowthrough only the first transistor (4526) when the pulse generator (4522)is generating a pulse and may flow only through the second transistor(4525) when the pulse generator (4522) is not generating a pulse. Thismay allow for an alternating current to be generated in the transmissionportion (4516). While shown in FIG. 45B as having a pulse generator(4522) connected to first and second transistors, it should beappreciated that the controller may comprise a pulse generator connectedto an H-Bridge, a microcontroller, or the like.

The output signal produced by the controller (4514) may be transmittedto a microstimulator using transmission portion (4516). The transmissionportion (4516) may comprise one or more coils, ultrasound generators,light sources, or the like which may transmit the output signal. Forexample, as shown in FIG. 45B, the transmission portion (4516) maycomprise a tuning capacitor (4528) in series with a coil (4530). Thiscircuit may be tuned such that the pulses generated by the controller(4514) are transmitted at a specific frequency (e.g., 1 Mhz, or thelike).

FIG. 46 shows another variation of a controller circuit (4600) which maybe used to generate a periodic oscillating output signal. As shownthere, the controller circuit (4600) may comprise a voltage source(4602), a resistor (4604), a first capacitor (4606), a second capacitor(4614), a third capacitor (4616), a bipolar junction transistor (4608),a transmission coil (4610), and a choke (4612). The voltage source(4602) (e.g., a battery) may be connected in parallel with the resistor(4604) and the first capacitor (4606), and the base of the bipolarjunction transistor (4608) may be connected between the resistor (4604)and the first capacitor (4606). A first end of the voltage source (4602)may also be connected to the transmission coil (4610). A second end ofthe voltage source (4602) may also be connected to the choke (4612) andthe third capacitor (4616). The collector of the bipolar junctiontransistor (4608) may be connected to the transmission coil (4610) andthe second capacitor (4614), and the emitter of the bipolar junctiontransistor (4608) may be connected to the second capacitor (4614), thethird capacitor (4616), and the choke (4612).

When the voltage source (4602) is connected to the controller circuit(4600), the voltage source (4602) may charge the first capacitor (4606)until the bipolar junction transistor (4608) begins to conduct. Whilethe bipolar junction transistor (4608) is conducting, an oscillatingsignal may be passed through the transmission coil (4610) to produce anoscillating magnetic field. The frequency of the oscillating outputsignal may be determined by the inductance value of the transmissioncoil (4610) and the capacitance values of the second (4614) and third(4616) capacitors. The choke (4612) may provide DC-biasing duringgeneration of the oscillating output signal. The oscillating signal maycontinue until the first capacitor (4606) has discharged through thebipolar junction transistor (4608) and the bipolar junction transistor(4608) stops conducting. At this point, the voltage source (4602) mayrecharge the first capacitor (4606), thereby repeating the production ofthe oscillating output signal. In this way, the oscillating signal maybe continually produced at set intervals until the voltage source (4602)is disconnected or otherwise depleted. The resistance of the resistor(4604) may determine the rate at which first capacitor (4606) charges,which may determine the delay between subsequent administrations of theoscillating output signal. In some variations, the resistor (4604) maybe adjustable to vary the delay. Additionally, the capacitance of thefirst capacitor (4606) may at least partially determine the duration ofthe oscillating output signal. In some variations, the first capacitor(4606) may be adjustable to vary the oscillating output signal duration.

The voltage source (4602) may be selectively connected to the controllercircuit to determine when the oscillating output signal is produced bythe controller circuit (4600). For example, in variations where thecontroller circuit (4600) is incorporated into a patch having a releaseliner, such as described in more detail above, removal of the releaseliner may connect the voltage source (4602) to the controller circuit(4600) (or otherwise complete the circuit) to initiate the periodicgeneration of the transmission signal. In these variations, the voltagesource (4602) may comprise one or more batteries which may power thecontroller circuit (4600) for a set period of time (e.g., about fourhours, about eight hours, or the like). In other variations, thecontroller may be configured to disconnect the voltage source (4602)after a set period of time (or upon some input from a patient). In somevariations, the controller may comprise one or more controllers and/oruser inputs which may control the connection of the voltage source(4602) to the controller circuit (4602).

In some variations, a controller may be configured to output a signalindependent of any feedback from an implanted micro stimulator (oranother controller). For example, in some variations, a controller maybe configured to produce a pre-set signal for a pre-set amount of timewhen the controller is activated (e.g., by depressing a button on thecontroller, removing a release liner from an adhesive layer, or thelike). In some variations, as will be described in more detail below,the pre-set signal may be modified by user input.

In other variations, a controller may be configured to alter its outputin response to feedback received from an implanted microstimulator. Insome instances, a controller may be configured to alter its output basedon feedback to account for misalignment or other movement between thecontroller and the microstimulator. For example, in some variations, theimplanted microstimulator may be configured to transmit to thecontroller information regarding the strength of the signal received bythe microstimulator, and the controller may be configured to alter itsoutput in response to the received information. In other variations, thecontroller may be configured to detect and measure a load positionedwithin a field produced by the controller, and may alter the strength ofthe produced field as a function of the measured load. Additionally oralternatively, the controller may be configured to receive one or moresignals measured from the patient (e.g., a signal indicative of drynessof the eyes), and may be configured to alter the output of thecontroller in response to the measured signal. In variations where theimplanted microstimulator comprises one or more adjustable/tunablecomponents, altering the output of the microstimulator may compriseadjusting the adjustable components.

In still other variations, it may be desirable to allow for a patient toalter the intensity of stimulation by increasing or decreasing theoutput strength of the controller. In some variations, a controller maycomprise one or more buttons, sliders, levers, knobs, or othermechanisms a patient may manipulate to alter the output strength of thecontroller. In other variations, a stimulation system may comprise oneor more external programmers which may be used to alter the output ofthe controller. For example, the hand-held controller (2102) describedabove in relation to FIG. 21 may be configured to communicate with andprovide programming instructions to one or more other controllers (e.g.,an implanted controller).

In some variations, a controller may comprise one or more safetyelements. For example, in some variations a controller may comprise atemperature sensor which measures the temperature inside the controller.In these variations, the controller may be configured to shut down whenthe temperature inside the controller exceeds a certain threshold. Thismay prevent the controller from reaching a temperature which may injurea patient (e.g., when the patient is holding the controller, when thecontroller is attached to the patient, etc.).

In some variations, a stimulation set may comprise a plurality ofcontrollers, wherein each controller is configured to produce adifferent output signal. FIG. 24 shows one variation of a controller set(2400), which comprises a plurality of individual controllers. As shownthere, controller set (2400) comprises a first controller (2402), asecond controller (2404), a third controller (2406), and a fourthcontroller (2408), although it should be appreciated that a controllerset (2400) may comprise any suitable number of controllers. Thecontrollers of the controller set (2400) may be configured to generateoutput signals having different stimulation parameters (e.g., pulsewidth, stimulation duration, etc.), such that a patient may select aspecific controller to achieve a certain physical effect. For example,the first controller (2402) may be configured to generate an outputsignal having a longer pulse width than an output signal generated bythe second controller (2404), and the second controller (2404) may beconfigured to generate an output signal having a longer pulse width thanan output signal generated by the third controller (2406). A patient mayuse the second controller (2404) to provide a stimulation signal to animplantable micro stimulator. If the stimulation is too intense for thepatient, the patient may switch the second controller (2404) for thethird controller (2406) (or the fourth controller (2408), which mayproduce a weaker stimulation signal than the third controller (2406)).Conversely, if the stimulation provided by the second controller (2404)does not achieve the desired physical effect, the patient may switch thesecond controller (2404) for the first controller (2402).

In some instances, it may be desirable to deliver a particularstimulation signal to a patient for a predetermined amount of time.Accordingly, it may be desirable to configure the stimulation system toprovide a controlled “dose” of stimulation to a patient. For example, itmay be desirable to configure a stimulation system to providestimulation for a set period of time (e.g., four hours, eight hours,twelve hours or the like). Accordingly, the controllers described heremay be configured to generate an output signal for a predeterminedperiod of time, which may result in the generation of a correspondingstimulation signal by a microstimulator implanted in the patient.

In variations where a controller comprises a patch having an adhesivelayer covered by a release line, such as those described in more detailabove, the removal of the release liner may initiate a dose ofstimulation therapy. In variations where a stimulation system comprisesa microstimulator having a passive stimulation system, the stimulationtherapy may comprise generating and transmitting an output signal to amicrostimulator, as described in more detail above. In variations wherea stimulation system comprises a microstimulator having an implantablepulse generator, the stimulation therapy may comprise delivering one ormore signals to the implantable pulse generator instructing themicrostimulator to deliver stimulation to tissue. The controller maycontinue to output the signal or signals for the duration of the dose ofstimulation therapy. In some instances, the controller may be programmedto shut down or otherwise cease producing signals after a set period oftime. In other instances, a power source of the controller may only havesufficient charge to power the controller for the duration of the doseof stimulation therapy.

In variations where a patch controller has a plurality of adhesivelayers separated by release liners, removal of each release liner maybegin a different dose of stimulation therapy. For example, it may bedesirable for a patient to receive one dose of stimulation therapy eachday. To begin a stimulation dose on the first day, a patient may removea first release liner from a first adhesive layer and may affix thecontroller to a skin surface via the first adhesive layer. Removal ofthe first release liner may initiate a first dose of stimulationtherapy, which may be delivered to the patient while the controller isaffixed thereto. The patch may be removed from the patient followingadministration of the first dose. On the next day, the patient mayremove a second release liner from a second adhesive layer (which mayinitiate a second dose of stimulation therapy), and may reaffix thecontroller to the skin surface to allow for delivery of the second doseof stimulation therapy. This may be repeated until each of the adhesivelayers of the patch controller has been used, or until the patient hasadministered a prescribed number of doses.

In other variations, a plurality of disposable controllers may be usedto deliver a plurality of doses of stimulation therapy. For example,FIGS. 25A and 25B show a side view and a top view of a controller set(2500) which may be used to deliver a plurality of doses of stimulationtherapy. As shown there, controller set (2500) may comprise a pluralityof stacked patch controllers (2502) attached to a base (2504). Eachpatch controller (2502) may comprise a tab (2506) or other structurewhich may aid in removal of that controller from the stack. In someinstances, one or more portions of each controller (2502) (e.g., the tab(2506)) may be labeled with a time or day for intended use of thatcontroller (2502), and that controller (2502) may be configured toprovide an output signal configured to provide a desired treatment forthe time or day of intended use. For example, a set of seven controllersmay be labeled Monday through Sunday. The stack of controllers (2502)may be configured such that removal of a controller from the stackactivates the controller (2502) to direct the delivery of a dose ofstimulation therapy (e.g. initiates generation of an output signal).Removal of the controller from the stack may also expose an adhesivelayer that may be used to affix the patch controller to a skin surfaceof the patient. After the controller has completed its dose ofstimulation therapy, the controller may be removed and discarded, and anew controller may be removed from the stack when it is desired todeliver a new dose of stimulation therapy.

While the controller set (2500) shown in FIGS. 25A and 25B comprises astack of controllers, it should be appreciated that in some variationsthe plurality of disposable controllers need not be directly connected.For example, FIG. 26 shows another variation of a controller set (2600)in which a plurality of patch controllers (2602) are each attached to abase (2604). Each of the controllers (2602) may be configured toactivate when removed from the base (2604) to direct the delivery of adose of stimulation therapy, and may be affixed to a patient via anadhesive layer that becomes exposed when the controller (2602) isremoved from the base (2604). In some of these variations, thecontroller set (2600) may comprise controllers (2602) that areconfigured to provide different doses of stimulation therapy. Forexample, some controllers of the set may be configured to providedifferent stimulation strengths and/or stimulation durations, such thata user may select a specific controller from the controller set (2600)depending on the desired stimulation.

As mentioned above, the controllers described here may be disposable, ormay be reusable. In some variations, the controller may be configured toprevent tampering or other modification of device components. Forexample, in some variations one or more components of the controller(e.g., a battery, a coil, or the like) may be welded to or otherwiseintegrally formed within the controller body such that accessing and/orremoving one or more of these components may disable functionality ofthe device. This may prevent a user from improperly trying to replace ormodify one or more components of the controller. In some variations, thecontroller may be configured such that one or more components of thecontroller is disposable, while one or more components of the controlleris reusable. For example, in some variations a controller may beconfigured such that one or more components of the controller, such as abattery, adhesive layer, or coil, may be replaced without needing toreplace the entire controller.

Methods

Also described here are methods for stimulating tissue. In somevariations, one or more of the stimulation systems described here may beused to deliver stimulation to one or more anatomical targets.Generally, a microstimulator of the stimulation system may be implantedwithin the patient, and may be used to generate a stimulation signalwhich is applied to tissue (e.g., via one or more electrodes). In somevariations, the microstimulator comprises a passive stimulation circuit,and the stimulation signal is passively generated from an output signalgenerated by a controller. The stimulation systems and associatedmethods may be used to treat one or more conditions. In some variations,the stimulation systems may be configured to treat one or more ocularconditions. For example, the stimulation systems described here may beconfigured to treat dry eye.

For the purposes of illustration, FIGS. 27A-27D depict various views ofthe anatomy of the head of a patient. FIG. 27A illustrates the lacrimal(or lachrymal) apparatus, the physiological system that contains thestructures of the orbit for tear production and drainage. Shown there isan eye (2730) having an upper lid (2720) and a lower lid (2722). Thelacrimal apparatus includes a lacrimal gland (2710), ducts (2712),puncta (2716), lacrimal ducts (2718), and nasolacrimal duct (2724). Thelacrimal gland (2710) may be innervated by several nerves. These nervesmay include the rami lacrimales, the lacrimal nerve, perivascular nervesof lacrimal artery, and sympathetic nerves fibers and neurites whichinnervate the lacrimal gland and its associated vasculature. Thelacrimal gland (2710) may secrete lacrimal fluid (i.e., tears) (2714)which may flow through the ducts (2712) into the space between the eye(2730) and the upper (2720) and lower (2722) lids. When the eye (2730)blinks, the lacrimal fluid (2714) may be spread across the surface ofthe eye (2730). The lacrimal fluid (2714) may collect in the lacrimallake (not shown), and may be drawn into the puncta (2716) by capillaryaction. The lacrimal fluid (2714) may flow through lacrimal canaliculi(not shown) at the inner corner of the upper (2720) and lower (2722)lids to enter the lacrimal ducts (2718) and drain through to thenasolacrimal duct (2724). The lacrimal fluid may drain from thenasolacrimal duct (2724) into the nasal cavity of the patient.

FIG. 27B illustrates additional anatomical structures around thelacrimal apparatus. As shown there, the rim of the upper lid (2720) andthe lower lid (2722) contain meibomian glands (2728). The meibomianglands (2728) are sebaceous glands responsible for the supply of meibum(an oily substance that includes lipids and slows evaporation of theeye's tear film). Also shown in FIG. 27B is the posterior lacrimal crest(2734), which is a vertical ridge that divides the orbital surface ofthe lacrimal bone into two parts. In front of the posterior lacrimalcrest (2734) is a longitudinal groove which unites with the frontalprocess (2746) of the skull (2740).

There are two bony depressions in the orbital cavity that may bereferred to as the lacrimal fossa. The first is a smooth, concaveshallow depression located on the inferior surface of each orbital plateof the frontal bone. This depression houses the lacrimal gland and isreferred to as the “fossa for the lacrimal gland” (2730). The second isa smooth, more deeply concave depression on the lacrimal bone, whichforms the medial wall of the orbital cavity. This depression houses thelacrimal sac and is referred to as the “fossa for the lacrimal sac”(2732).

The supraorbital process (2744) is a passage in the frontal bone for thesupraorbital artery and nerve. The supraorbital process (2744) islocated on the superior and medial margin of the orbit in the frontalbone. The orbit of the skull (2740) is lined with a periosteum (notshown) and contains the eye (2730), extraocular muscles for movement ofthe eye (2730), veins (not shown), arteries (not shown), and nerves (notshown) which traverse the orbit into the face and the lacrimal gland(2710).

The extraocular muscles include the lateral rectus (2750), the medialrectus (not shown), the superior rectus (2752), inferior rectus (2754),superior oblique (2756), inferior oblique (2758), and the levatorpalpebrae superioris (not shown). The lateral rectus (2750) abducts theeye away from the nose and the medial rectus adducts the eye towards thenose. The lateral rectus (2750) and the medial rectus move the eye onlyin a horizontal plane. The superior rectus (2752), inferior rectus(2754), superior oblique (2756), and inferior oblique (2758) controlvertical motion. The levator palpebrae superioris originates on thesphenoid bone (2736) and is responsible for elevating the upper lid(2720). The malar process (2726) is a rough projection from the maxilla(not shown) that articulates with the zygomatic bone (2770).

FIG. 27C shows a front view of the skull, and emphasizes the anatomy ofthe orbit with respect to the bones of the skull (2740). FIG. 27D showsan enlarged view of the left orbit of the skull (2740). As shown there,the exterior to the orbit includes the posterior lacrimal crest (2734),the supraorbital process (2744), the frontal process (2746), thesphenoid bone (2736), and the zygomatic bone (2770). The interior of theleft orbit includes the superior orbital fissure (2733), inferiororbital fissure (2735), the fossa for the lacrimal gland (2780) and thefossa for the lacrimal sac (2732). The structures that enter the orbitthrough the superior orbital fissure 33 include the cranial nerves (CN)III, IV, and VI, lacrimal nerve, frontal nerve, nasociliary nerve,orbital branch of middle meningeal artery, recurrent branch of lacrimalartery, superior orbital vein, and the superior ophthalmic vein. Thestructures that enter the orbit through the inferior orbital fissure 35include the infraorbital nerve, zygomatic nerve, parasympathetics to thelacrimal gland, infraorbital artery, infraorbital vein, and inferiorophthalmic vein branch to pterygoid plexus.

FIG. 28 depicts a flow chart of a method for stimulating an anatomicaltarget using the stimulation systems described here. This method may beused to treat dry eye, or one or more other conditions as described inmore detail below. First, a microstimulator may be implanted using aninsertion device at step (2800). The microstimulator may be any suitablemicrostimulator, such as one or more of the microstimulators describedin more detail above. The microstimulator may comprise a passivestimulation circuit, but need not. In variations where themicrostimulator comprises a passive stimulation circuit, the passivestimulation circuit may comprise a ramping control unit which maypassively ramp a stimulation signal produced by the passive stimulationcircuit, as described in more detail below.

The insertion device may be removed from the patient at step (2802). Awaveform signal may be generated at step (2804). The waveform signal maybe generated as an output signal of a controller. The waveform may begenerated automatically based on closed loop control or based on userinput received by the controller. A stimulation signal may be generatedfrom the waveform signal at step (2806). The stimulation signal may begenerated by a microstimulator based on the output signal generated bythe controller and received by the microstimulator. The stimulationsignal may then be applied to the anatomical target at step (2808).

When implanting a microstimulator as mentioned in relation to step(2800), the microstimulator may be implanted at any suitable locationrelative to the body. In some variations, the microstimulator may beimplanted in the orbit of the skull adjacent to the eye. In somevariations, the microstimulator may be implanted into about, inproximity to, within or partially in the lacrimal gland. In somevariations, the microstimulator may be implanted into the fossa for thelacrimal gland. In instances where the microstimulator is used to treatdry eye, the microstimulator may be used to stimulate one or more nervesthat innervate the lacrimal gland tissue, as will be described in moredetail below.

FIGS. 29A-29H depict different implantation locations which may allow amicrostimulator to stimulate the lacrimal gland (e.g., for the treatmentof dry eye). FIG. 29A shows a medial view of an eye within the orbit ofa patient's skull. The view of FIG. 29A corresponds to the view line 29Aillustrated in FIG. 27C. Specifically, FIG. 29A includes the eye (2730)with upper lid (2720) and lower lid (2722), superior rectus (2752),lateral rectus (2750), inferior rectus (2754), and the lacrimal gland(2710) of FIG. 27C. Also shown there is the orbital process (2742) ofthe zygomatic bone, which is a thick, strong plate, projecting backwardand medialward from the orbital margin.

As shown in FIG. 29A (and in an enlarged view in FIG. 29B), amicrostimulator (2900) may be positioned between the portion of the boneforming the fossa for the lacrimal gland (2780) and the periosteum(2922). The periosteum (2922) of the orbit of a healthy eye may betightly attached. In cases of a diseased eye, the periosteum (2922) maybe loosely attached and raised from the bone beneath.

FIG. 29C shows another section medial view of an eye within the orbit ofa patient's skull. The view of FIG. 29C corresponds to the view line 29Cillustrated in FIG. 27C. The view of FIG. 29A is lateral and more medialthan the view FIG. 29C. FIG. 29C includes the eye (2730) with upper lid(2720) and lower lid (2722), superior rectus (2725), lateral rectus(2750), inferior rectus (2754), and the lacrimal gland (2710). In somevariations, as shown in FIG. 29C (and in an expanded view in FIG. 29D) amicrostimulator (2924) may be positioned between the periosteum (2922)and the portion of the bone forming the fossa for the lacrimal gland(2780), such as shown in FIGS. 29A and 29B.

FIG. 29E is another section medial view of an eye within the orbit of apatient's skull. The view of FIG. 29E corresponds to the view line 29Eillustrated in FIG. 27C. As shown in FIG. 29E (and in an expanded viewin FIG. 29F), in some variations a microstimulator (2926) may bepositioned between the periosteum (2922) and the lacrimal gland (2710).

FIG. 29G is another section medial view of an eye within the orbit of apatient's skull. The view of FIG. 29G corresponds to the view line 29Gillustrated in FIG. 27C. FIG. 29H is another enlarged section view ofthe inferior edge of the superior orbit having a microstimulator (2928).The position of microstimulator (2928) is similar to the positioning ofmicrostimulator (2924) shown FIGS. 29C and 29D, except that themicrostimulator (2928) is shown positioned between the periosteum (2922)and the lacrimal gland (2710).

FIG. 32 illustrates another implant zone (3200) for a microstimulator(not shown) or for one or more electrodes of a microstimulator. Themicrostimulator or electrodes thereof may be positioned within the fossafor the lacrimal gland of the orbit between the superior rectus muscle(3202) and the lateral rectus muscle (3204) of the eye (3205). Whenpositioned there, the microstimulator may selectively stimulate ananatomical target such as a lacrimal gland (3206) without fullyactivating the extraocular muscles. For example, stimulation of thelacrimal gland may be sufficient to produce lacrimation or vasodilationof glandular blood vessels without engaging the extraocular muscles thatwould move the eye in a horizontal or vertical direction.

The microstimulators or electrodes thereof may be positioned in oradjacent to any of the bony structures and regions of the skull thatprovide access to one or more of the anatomical targets specific to theprocess of lacrimation, such as those shown in FIG. 27D. Some of thebony structures and regions include, but are not limited to, thesphenoid bone (2736), inferior orbital fissure (2735), the infraorbitalforamen (2762), the maxillary axis (2764), the nasal-maxillary area(2766), the nasal cavity (2768), the fossa for the lacrimal sac (2732),the posterior lacrimal crest (2734), the inferior medial aspect of thesupraorbital process (2772), the superior orbital fissure (2733) and thefossa for the lacrimal gland (2780).

In some variations, one or more microstimulators may be positioned on asurface of the eye, such as microstimulator (620) described above withrespect to FIG. 6G. Additionally or alternatively, one or moremicrostimulators or electrodes therein may be positioned in one or morepuncta, lacrimal ducts and/or nasolacrimal ducts. For example, FIG. 33shows one variation in which a microstimulator (3300) is positioned atleast partially within a lacrimal duct (3302). In these variations, acurrent may be delivered to one or more afferents (e.g., afferents inthe ocular surface, afferents in the lacrimal or nasolacrimal ducts),which may result in reflexive tear production. The microstimulator(3300) may be any of the microstimulators described in more detailabove, and may be powered in any suitable manner as described in moredetail above.

It should be appreciated that any of the microstimulators describedabove may be implanted on or adjacent an anatomical target such as alacrimal gland. FIGS. 31A-31D illustrate different variations ofmicrostimulators which are positioned on or adjacent a lacrimal gland ofa patient. FIG. 31A is a perspective view of a patient's eye with onevariation of a microstimulator (3100). The microstimulator (3100) may bea planar pliable microstimulator, such as the microstimulator (606)discussed above with respect to FIG. 6D. The planar pliable device isshown in FIG. 31A as being positioned on or adjacent to the lacrimalgland (3102) and has been unfurled such that a surface of themicrostimulator expands over a portion of the surface of the lacrimalgland.

FIG. 31B is a perspective view of a patient's eye with another exemplarymicrostimulator (3104). The microstimulator (3104) may be a curved microstimulator, such as the microstimulator (604) discussed above withrespect to FIG. 6B. The curved microstimulator (3104) positioned on oradjacent the lacrimal gland (3102) and curves to conform to ananatomical structure of a patient, such as the fossa for the lacrimalgland.

FIG. 31C is another perspective view of a patient's eye with anexemplary microstimulator (3106). The microstimulator (3106) maycomprise a flexible segmented microstimulator, such as microstimulator(608) shown in FIG. 6E. The microstimulator (3106) may comprise a curvedshape which may conform to an anatomical structure of a patient, such asa fossa for a lacrimal gland, and may comprise a plurality of electrodes(3108) as described in more detail above.

FIG. 31D is another perspective view of a patient's eye with themicrostimulator (4200) described above in relation to FIGS. 42A-42C. Asshown there, the microstimulator (4200) may be position on or adjacentthe lacrimal gland (3102), such that the first (4206) and second (4208)electrodes are facing the lacrimal gland (3102). In some instances, asshown in FIG. 31D, the microstimulator (4200) may be positioned firstelectrode (4206) is distally of the second electrode (4208) relative tothe upper lid (3110). In these variations, tissue stimulating currentsmay be directed out of the first electrode (4206), which may reduceextraneous tissue stimulation around the conjunctiva (3112).Additionally, as shown in FIG. 31D, the housing (4202) (or another end)of the microstimulator (4200) may be positioned against or near theconjunctiva (3112), which may facilitate retrieval of themicrostimulator. For example, the housing (4202) of the microstimulator(4200) may be positioned such that it is visible through the conjunctivawhen the upper lid (3110) is lifted. In some variations, one or moreportions of the microstimulator (4200) may be colored to increase thevisibility of the microstimulator (4200). To remove the microstimulator(4200), a physician may cut the conjunctive overlying themicrostimulator (4200), and may grasp the microstimulator (4200) with aretrieval tool such as forceps.

While discussed above as being implanted in, on, or near one or morestructures around the ocular cavity, it should be appreciated thatmicrostimulators described here may be implanted in any suitablelocation. In some variations, a microstimulator may be implanted in alocation to provide stimulation to one or more target nerves. Forexample, the microstimulator may be positioned to stimulate an occipitalnerve (e.g., to treat headache or other pain), a vagus nerve (e.g., totreat epilepsy, depression, or the like), a dorsal genital nerve (e.g.,to treat erectile or sexual dysfunction, urinary incontinence, or thelike), or the like. When positioned to stimulate a nerve, in someinstances the electrodes of the microstimulators may be located on theepineurium of a nerve or away from the portion of the nerve thatinnervates tissue or gland. An example of a direct nerve stimulator is anerve cuff which includes electrodes carried on the inside walls of acylindrical polymeric sheath. The nerve cuff may be wrapped around thenerve to bring the electrodes into direct contact with an isolatedportion of a nerve to be stimulated. Indirect stimulation of a nerve mayinclude delivering low amplitude electrical stimulation via electrodesthat are in close proximity, but not in direct contact, with the nerveto be stimulated. Nerves that are in a bundle, plexus or innervatingtissue or a gland are not isolated from other nerves or structures.Target nerves or structures that are not isolated may stimulatedindirectly by using electrical selectivity.

In other variations, one or more microstimulators may be implanted inone or more locations in or around the mouth or salivary glands. Forexample, in some variations a microstimulator may be positioned in, on,or around a submandibular gland, a parotid gland, a sublingual gland, orthe like. In these variations, the stimulation systems may be used toprovide stimulation (as described hereinthroughout) to one or more ofthese anatomical targets to treat one or more conditions such as drymouth. The microstimulator may be implanted using any suitable approach.For example, in some variations, a microstimulator may be placedsubcutaneously to position the microstimulator in, on, or around thesublingual gland. When positioning a microstimulator in, on, or aroundthe submandibular gland or the sublingual, the microstimulator may beadvanced through the floor of the mouth, or may be advanced using asubmandibular approach. The microstimulator may be delivered using oneor more of the delivery systems described above.

The microstimulators described here may be delivered in any suitablemanner. Described here are delivery systems and methods for delivering amicrostimulator to a region of tissue. The delivery systems generallycomprise at least one insertion device, and in some variations maycomprise a dissection tool. Delivery of the microstimulators may be doneunder direct visualization and/or indirect visualization (e.g.,ultrasound, fluoroscopy, or the like). FIG. 34 illustrates one instancein which an insertion device (3400) may be used to implant amicrostimulator (3402) into a patient. As shown there, the insertiondevice (3400) may insert the microstimulator (3402) through an insertionregion near the fossa for the lacrimal gland. In some variations, themicrostimulator (3402) may be secured within the insertion device (3400)while being positioned within the patient. Once the insertion device haspositioned the microstimulator (3402) at a desired location within thepatient, the insertion device (3400) may deploy the microstimulator(3402) in the patient.

FIG. 35A shows a side view of one variation of an insertion device(3500) which may be used to deliver a microstimulator (3502). As shownthere, the insertion device (3500) includes a housing (3524), a distalend (3526), and a device shaft (3528). The microstimulator (3502) may besecured near the distal end (3526) of the insertion device (3500).Insertion device (3500) may position the microstimulator (3502) at oradjacent an anatomical target, such as a lacrimal gland, within apatient while the microstimulator (3502) is secured to the insertiondevice (3500). In some variations, the insertion device (3500) mayinclude a needle (e.g., a 12 or larger gauge needle). As shown in FIG.35B, microstimulator (3502) may be released from the insertion device(3500) by withdrawing the device housing (3524) relative to the deviceshaft (3528) (or by advancing the device shaft (3528) relative to thedevice housing (3524)). In some variations the insertion device (3500)may contain elements for positioning the insertion device in a locationwhich facilitates safe and accurate delivery of the microstimulator(3502). The insertion device may house the microstimulator (3502) in anon-needle cannula.

The insertion device may contain one or more energy storage devices tofacilitate insertion, for example a spring. The insertion device maycontain an element by which the implanting physician triggers theinsertion or deployment of the microstimulator, such as a plunger orbutton. FIG. 38 shows one such variation of an insertion device (3800)that may be used to deliver a microstimulator (3802), which may one ormore of the microstimulators described above. As shown there, theinsertion device (3800) may comprise a housing (3804) having a pistonassembly (3806) and a spring (3808) housed therein, and a trigger member(3810). The spring (3808) may connect a portion of the piston assembly(3806) to the housing (3804), such that energy stored in the spring(3808) may move the piston assembly (3806) relative to housing (3804).For example, as shown in FIG. 38, the piston assembly (3806) may beretracted such that the spring (3808) may be stretched, and the pistonassembly (3806) may be held in a cocked position (e.g., via the triggermember (3810)). The trigger member (3810) may be actuated to release thepiston assembly (3806) relative to the housing (3804). The spring (3808)may then bias towards an unstretched configuration, which may pull thepiston assembly (3806) towards the distal end of the insertion device(3800). As the piston assembly (3806) moves forward, it may advance themicrostimulator (3802) out of the housing (3804), thereby delivering themicrostimulator (3802). While shown in FIG. 38 as being stretched whenthe piston assembly (3806) is cocked, in some instances the spring(3808) may be configured such that it is compressed when the pistonassembly (3806) is cocked.

In some variations, the delivery systems may comprise one or moredissection tools which may be used to form an insertion pathway fromoutside a patient to a delivery location for a microstimulator. Forexample, FIG. 39 shows one variation of a dissection tool (3900) whichmay be used to form an insertion pathway into the orbit of the eye. Asshown there, the dissection tool (3900) may comprise a base member(3902) and an insertion portion (3904). The insertion portion (3904) mayinclude a cutting edge (3906) at a distal end thereof, which may severtissue as the dissection tool (3900) is advanced into tissue. Thecutting edge (3906) may include a single bevel, double bevel, a roundedpoint, or the like. While shown in FIG. 39 as having a single cuttingedge (3906), it should be appreciated that in some instances thedissection tool (3900) may comprise two or more cutting edges, which mayhelp the dissection tool (3900) to maintain an intended course duringadvancement. In some variations, the insertion portion (3904) maycomprise a curved section (3908) which may allow the insertion portion(3904) to curve around the bony socket of the skull during insertion.Additionally or alternatively, in some variations, the insertion portion(3904) may be angled relative to the base member (3902). The anglebetween the insertion portion (3904) and the base member (3902) may beany suitable angle (e.g., between about 10 degrees and about 170degrees), and may allow a physician easier access to the orbit with theinsertion portion (3904) without the base member (3902) being blocked orimpeded by the cheek or another portion of the face. In the variation ofdissection tool (3900) shown in FIG. 39, base member (3902) may comprisean aperture (3910) which may allow the dissection tool to be connectedto a handle (e.g., a scalpel handle, an insertion device, or the like).In other variations, the dissection tool may comprise a handleintegrally connected to the base member. Additionally or alternatively,in some variations, a portion of the dissection tool (3900) may beconfigured to vibrate during advancement to assist in cutting tissue.

FIGS. 40A-40D illustrate a method by which a microstimulator may beplaced on or adjacent the lacrimal gland using the delivery systemsdescribed here. Initially, the upper lid (4002) may be lifted relativeto the eye (4000), as shown in FIG. 40A, which may reveal theconjunctiva. In some variations, the lid may be held open by hand, orusing one or more tools. In some variations an insertion device ordissecting tool may comprise one or more components which may hold thelid in a lifted configuration. The physician may locate the lacrimalgland visually and/or or using one or more indirect visualization, andmay advance a dissection tool (4008) to cut the conjunctiva and form aninsertion pathway between the lacrimal gland (4004) and the orbit(4006), as shown in FIG. 40B. The dissection tool (4008) may be anysuitable dissection tool, such as the dissection tool (3900) describedabove in relation to FIG. 39. In some variations, the dissection tool(4008) may be advanced such that it cuts through a portion of theperiosteum (not shown) and the insertion pathway is formed between theperiosteum and the orbit (4006). In other variations, the dissectiontool (4008) is advanced such that it does not cut through the periosteumand the insertion pathway is formed between the periosteum and thelacrimal gland (4004). In still other variations, the insertion pathwaymay be formed in a portion of the lacrimal gland (4004), which may allowa portion of the microstimulator to be positioned within the lacrimalgland.

Once an insertion pathway is formed, an insertion device (4010) may beadvanced through the insertion pathway. In some variations, thedissection tool (4008) may be partially or fully withdrawn prior toadvancing the insertion device (4010). In some variations, the insertiondevice (4010) is advanced along the dissection tool (4008) to introducethe insertion device (4010) at least partially into the insertionpathway, as shown in FIG. 40C. Once the insertion device (4010) is inplace, a microstimulator (4012) may be delivered from the insertiondevice (4010) into the insertion pathway, and the delivery tools may beremoved, as shown in FIG. 40D. In some variations, the insertion devicemay not be introduced into the insertion pathway, but may instead pushor otherwise advance the microstimulator (4012) into the insertionpathway over the dissection tool (4008).

While the dissection tool (4008) is shown in FIGS. 40A-40D as beingseparate from the insertion device (4010), it should be appreciated thatin some variations an insertion device may comprise a dissection toolcomponent which may create an insertion pathway. In other variations,the dissection tool may be configured to house and eject amicrostimulator, such that the dissection tool may be configured todeliver the microstimulator.

In some variations, the delivery systems may comprise a guiding elementfor helping to direct or otherwise position one or more dissection toolsand/or insertion devices of the delivery system. For example, FIG. 41depicts one variation of a guiding element (4100) suitable for use withthe delivery systems described here. As shown there, the guiding element(4100) may comprise a base (4101) and a guide cannula (4102) extendingtherefrom. The guide cannula (4102) may comprise a lumen (4104)extending through the guide cannula (4102) and the base (4101), suchthat one or more delivery tools (e.g., a dissection tool, an insertiondevice, or the like) may be advanced therethrough. The base (4101) maybe positioned on one or more surfaces of the patient (e.g., over theeye, on the forehead, on the cheek, combinations thereof or the like) toalign the guide cannula (4102) with an insertion site for themicrostimulator. In some variations, the angle or pitch of the guidecannula (4102) relative to the base may be adjustable. Once the guidecannula (4102) is aligned with the intended insertion site for themicrostimulator, one or more delivery tools may be advanced through thelumen (4104) to deliver a microstimulator to the insertion site, asdescribed in more detail above. As the delivery tools are passed throughthe lumen (4104), the guide cannula (4102) may act to align the deliverytools relative to the insertion site. This may help provide moreaccurate placement of the microstimulator relative to tissue.Additionally, when placed over one or more structures of the body (e.g.,the eye), the base (4101) may protect these bodily structures and mayprevent unintended damage to tissue.

Either during or after placement of the microstimulator, a physician maytest one or more stimulation parameters of the stimulation system. Forexample, a test signal may be applied to the patient using themicrostimulator, one or more electrodes incorporated into the deliverysystem, a percutaneous needle stimulator, or the like. The physician mayassess one or more outcomes of the test signal, such as tear production,discomfort, sensation, or the like), and may alter stimulationparameters and/or positioning of the device. For example, in somevariations, the microstimulator may be repositioned if the test signaldoes not result in adequate tear production, or if the test signalresults in discomfort in the patient. Additionally or alternatively, oneor more stimulation parameters (e.g., pulse width, amplitude, etc.) maybe adjusted depending on the results of the test signal. In somevariations, this may comprise adjusting one or more adjustable elementsof the microstimulator, as described in more detail above. Thestimulation parameters and/or positioning of the microstimulator may berepeated as necessary to achieve a desired stimulation outcome.

Once the microstimulator is in place relative to the body, themicrostimulator may be used to deliver stimulation to one or moretissues. For example, when used to treat dry eye, stimulation may beapplied to the lacrimal gland. The stimulation may selectively stimulateone or more nerves that innervate the lacrimal gland. In somevariations, the stimulation only stimulates one or more nerves thatinnervate the lacrimal gland. In other variations, the stimulation maybe applied to tissue in or around the puncta, lacrimal ducts and/ornasolacrimal ducts.

When stimulating one or more of the nerves or tissues described above,it may be desirable to stimulate these nerves without stimulating theocular muscles discussed above. The autonomic efferent fibers may beselectively stimulated over the sensory afferent fibers and the A-deltapain fibers. The efferent fibers may be selectively stimulated over theC pain fibers. In some variations it may be desirable to select a pulsewidth that stimulates efferent fibers over pain fibers. In some of thesevariations, stimulation using short pulse widths (e.g., 50 μsec-300μsec) may bias stimulation toward efferent fibers.

The stimulation signal produced by the microstimulator may include apulse amplitude, a pulse width, and a pulse frequency. One or more ofthe pulse amplitude, pulse width, or pulse frequency may be varied overthe treatment period. The stimulation signal may include a currenthaving a pulse amplitude between about 500 μA to about 25 mA. Thestimulation signal may have a pulse frequency between about 2 Hz toabout 200 Hz. The pulse frequency may be between about 30 Hz to about 40Hz. The stimulation signal may include a current having a pulse widthbetween about 50 μsec to about 2000 μsec. In some variations, thestimulation may be adjusted in response to a measured variable. Thestimulation signal may be delivered in bursts and may include a currenthaving a pulse width between about 100 μsec to about 1000 μsec.Stimulation using these stimulation parameters may be used to treat dryeye, as described herein.

The stimulation may be delivered in a pattern. The patterned stimulationmay be used to ensure the comfort of the patient. The patternedstimulation may be used to efficacy of the stimulation. The stimulationmay be delivered periodically at regular or irregular intervals.Stimulation bursts may be delivered periodically at regular or irregularintervals. The stimulation amplitude, pulse width or frequency may bemodified during the course of stimulation. For example, the stimulationamplitude may be ramped from a low amplitude to a higher amplitude overa period of time. Stimulation amplitude may be ramped from a highamplitude to a lower amplitude over a period of time. Stimulation pulsewidth may be ramped from a low pulse width to a higher pulse width overa period of time. Stimulation pulse width may be ramped from a highpulse width to a lower pulse width over a period of time. The rampperiod may be between 1 second and 15 minutes. The ramp period may bebetween 5 seconds and 30 seconds. Stimulation may be delivered at nighttime. Stimulation may only be delivered at night time. Stimulation mayconsist of very high frequency pulses to block activity in the targettissue. These very high frequency pulses may be of a frequency between1,000 Hz and 100,000 Hz.

As mentioned above the stimulation provided by the microstimulator maybe generated in response to an output signal produced by a controller.In these variations, a controller may be activated to initiate theoutput signal of a controller, and the controller may be brought near areceiving portion of the microstimulator to transmit the output signalto the controller. In some variations, this may comprise connecting orotherwise affixing the controller to a portion of the anatomy. Forexample, in variations where a microstimulator is positioned in, on, oraround the lacrimal gland, a controller may be positioned near theocular cavity of the patient. For example, in variations where thecontroller comprises a patch, the patch may be positioned on the temple,brow, forehead, cheek, or other suitable location of the patient. Thepatch may be held in place via an adhesive (as described in more detailabove) or via one or more magnets in the controller (which may beattracted to one or more magnets positioned within the patient). Invariations where a stimulation system comprises an implanted controller,the controller may be programmed to output the output signal on a timedbasis and/or may be configured to produce an output signal in responseto a signal received from an external programmer.

When the stimulation systems described here are used to treat dry eye bystimulating one of the anatomical structures listed above, such as thelacrimal gland, it may be desirable to first evaluate whether the use ofthe stimulation systems described here is appropriate for a patient. Forexample, in some patients, the lacrimal gland may be irreparably damagedto the point where it is unable to secrete tears. In these variations, atest may be conducted to evaluate whether the lacrimal gland is capableof secreting tears. In some variations, one or more stimulation signalsmay be administered to the lacrimal gland prior to or during delivery ofa microstimulator. For example, a transcutaneous skin stimulator or apercutaneous needle stimulator may be used to provide a test signal tothe lacrimal gland, and a physician or other user may evaluate aphysiological response from the patient (e.g., tear production). Thetest signal may be configured such that if administration of the testsignal produces a physiological response from the patient, thentreatment using the stimulation systems described here is appropriatefor that patient. It should be appreciated that one or more electrodesmay be incorporated into one or more of the insertion devices describedabove, such that one or more test signals may be administered duringdelivery of a microstimulator to a patient.

When the stimulation systems and methods described above are used totreat dry eye, it should be appreciated that the stimulation provided bythe stimulation current may be configured to rehabilitate the lacrimalgland. In these variations, a treatment regimen may be supplied to thelacrimal gland to improve the functioning of the lacrimal gland overtime. In some instances, a treatment regimen may comprise stimulatingthe lacrimal gland at predetermined times (e.g., daily stimulation), orthe like. The stimulation provided by the microstimulator may compriseany suitable stimulation parameters, such as those described in moredetail above.

While the methods described above discuss delivering electricalstimulation to one or more anatomical tissues, it should be appreciatedthat the stimulation systems may additionally or alternatively stimulatetissue using one or more chemical, optical, magnetic, thermal, and/oracoustic stimulation. For example, when the methods described above areused to treat dry eye, it may be desirable to additionally oralternatively provide one or more drugs or active agents to one or moreof the anatomical structures described in more detail above (such as thelacrimal gland). The agents delivered may any suitable agent orcombination of agents (such as pilocarpine or one or moreparasympathetic agents), and may be delivered in any suitable manner. Insome variations, the microstimulator may be configured to release one ormore drugs or active agents therefrom. Additionally or alternatively, adrug-releasing implant may be delivered to the lacrimal gland, the fossafor the lacrimal gland, the formix, a lacrimal duct, the eye (e.g., viaa contact lens). For example, one or more biodegradable depotscomprising one or more agents (e.g., pilocarpine) may be implanted in,on, or near the lacrimal gland. The depot or depots may comprise onemore biodegradable polymers (e.g., PLA, PLGA, combinations thereof, orthe like), and may be configured to release the one or more agents overa certain period of time (e.g., one weeks, two weeks, one month, or thelike). Additional depots may be implanted to prolong administration ofthe one or more agents to the lacrimal gland.

In some variations, the methods described here may additionally compriseproviding optical stimulation to an anatomical target such as thelacrimal gland. For example, optical stimulation may comprisephoto-electric activation of a drug (such as a drug released from one ormore of the implants described above), infrared stimulation using aVanderbilt/Jensen technique, or the like, or therapy using anoptogenetics technique. In some variations, the methods described heremay additionally comprise providing magnetic stimulation to one or moreanatomical targets. For example, in some variations one or more externalmagnetic fields may be configured to induce a current in tissue. In somevariations, the methods described here may comprise increasing ordecreasing the temperature in or around a certain tissue to activate orotherwise assist in therapy of that tissue. In still other variations,the methods described here may comprise providing ultrasound or otheracoustic energy to an anatomical target.

The stimulation systems and methods described above may be used to treata number of conditions. For example, the stimulation devices describedhere may be used to stimulate one or more tissues in or around the eyeto treat one or more conditions, including but not limited to,allergies, amblyopia, Bell's Palsy, blepharitis, corneal ulcers, eyeocclusions, eye twitch, macular hole, nystagmus, ocular migraine, ocularrosacea, optic neuritis, photophobia, pinguecula, pterygium, ptosis,strabismus, uveitis, conjunctivitis, diabetic retinopathy, glaucoma(e.g., via ciliary body/nerve stimulation), keratoconus, maculardegeneration, macular dystrophy, ocular hypertension, retinitispigmentosa, Stargardt disease, diplopia, hyperopia, myopia, andpresbyopia.

What is claimed as new and desired to be protected by Letters Patent ofthe United States is:
 1. An implantable microstimulation unitcomprising: a housing comprising a stimulation circuit and a feedthroughat a first end of the housing, wherein the stimulation circuit does notinclude any internal logic or intelligence and does not have an internalbattery; and a flexible extension comprising at least one electrode andan energy-receiving inductive coil positioned within the flexibleextension, wherein the electrode is connectable to the stimulationcircuit via the feedthrough, and wherein the flexible extension has athickness that is less than a thickness of the housing and tapers to thethickness of the housing or has a thickness that is the same as thethickness of the housing, such that the first end of the housing and afirst end of the flexible extension have corresponding and complementaryshapes that connect to form the implantable microstimulation unit,wherein the implantable microstimulation unit has a length of about 0.6cm to about 2 cm, a thickness of about 1 mm to about 2 mm, and a widthof about 3 mm to about 8 mm.
 2. The implantable microstimulation unit ofclaim 1 wherein the at least one electrode comprises a first electrodeand a second electrode.
 3. The implantable microstimulation unit ofclaim 2 wherein the first and second electrodes are positioned on afirst side of the flexible extension.
 4. The implantablemicrostimulation unit of claim 2 wherein the first electrode ispositioned on a first side of the flexible extension, and the secondelectrode is positioned on a second side of the flexible extension. 5.The implantable microstimulation unit of claim 1, wherein at least oneof the at least one electrodes is textured or patterned.
 6. Theimplantable microstimulation unit of claim 1, wherein at least one ofthe at least one electrodes is recessed.
 7. The implantablemicrostimulation unit of claim 1 wherein the stimulation circuitcomprises a ramping control unit.
 8. The implantable microstimulationunit of claim 1 wherein the microstimulation unit comprises one or morecoatings.
 9. The implantable microstimulation unit of claim 8 wherein atleast one of the one or more coatings is configured to enhance chargeinjection capacity.
 10. The implantable microstimulation unit of claim 8wherein at least one of the one or more coatings is an insulatingcoating.
 11. The implantable microstimulation unit of claim 1 whereinthe microstimulation unit comprises one or more fixation elements. 12.The implantable microstimulation unit of claim 1 wherein the implantablemicrostimulation unit is configured to be positioned within an orbit ofa patient's eye.